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EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Small Proteome

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  • Authors: Matthew R. Hemm1, Jeremy Weaver2,3, and Gisela Storz4
  • Editors: Susan T. Lovett5, Deborah Hinton6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biological Sciences, Towson University, Towson, MD; 2: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 3: Present address: Thermo Fisher Scientific, Rockford, IL; 4: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 5: Brandeis University, Waltham, MA; 6: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
  • Received 08 December 2019 Accepted 27 February 2020 Published 08 May 2020
  • Address correspondence to Matthew Hemm, [email protected]
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  • Abstract:

    was one of the first species to have its genome sequenced and remains one of the best-characterized model organisms. Thus, it is perhaps surprising that recent studies have shown that a substantial number of genes have been overlooked. Genes encoding more than 140 small proteins, defined as those containing 50 or fewer amino acids, have been identified in in the past 10 years, and there is substantial evidence indicating that many more remain to be discovered. This review covers the methods that have been successful in identifying small proteins and the short open reading frames that encode them. The small proteins that have been functionally characterized to date in this model organism are also discussed. It is hoped that the review, along with the associated databases of known as well as predicted but undetected small proteins, will aid in and provide a roadmap for the continued identification and characterization of these proteins in as well as other bacteria.

  • Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019

References

1. Blattner FR, Plunkett G III, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y. 1997. The complete genome sequence of Escherichia coli K-12. Science 277:1453–1462 http://dx.doi.org/10.1126/science.277.5331.1453.
2. Keseler IM, Collado-Vides J, Gama-Castro S, Ingraham J, Paley S, Paulsen IT, Peralta-Gil M, Karp PD. 2005. EcoCyc: a comprehensive database resource for Escherichia coli. Nucleic Acids Res 33:D334–D337 http://dx.doi.org/10.1093/nar/gki108. [PubMed]
3. Keseler IM, Collado-Vides J, Santos-Zavaleta A, Peralta-Gil M, Gama-Castro S, Muñiz-Rascado L, Bonavides-Martinez C, Paley S, Krummenacker M, Altman T, Kaipa P, Spaulding A, Pacheco J, Latendresse M, Fulcher C, Sarker M, Shearer AG, Mackie A, Paulsen I, Gunsalus RP, Karp PD. 2011. EcoCyc: a comprehensive database of Escherichia coli biology. Nucleic Acids Res 39(Database) :D583–D590 http://dx.doi.org/10.1093/nar/gkq1143. [PubMed]
4. Tatusova T, DiCuccio M, Badretdin A, Chetvernin V, Nawrocki EP, Zaslavsky L, Lomsadze A, Pruitt KD, Borodovsky M, Ostell J. 2016. NCBI Prokaryotic Genome Annotation Pipeline. Nucleic Acids Res 44:6614–6624 http://dx.doi.org/10.1093/nar/gkw569. [PubMed]
5. Rudd KE, Humphery-Smith I, Wasinger VC, Bairoch A. 1998. Low molecular weight proteins: a challenge for post-genomic research. Electrophoresis 19:536–544 http://dx.doi.org/10.1002/elps.1150190413. [PubMed]
6. Weaver J, Mohammad F, Buskirk AR, Storz G. 2019. Identifying small proteins by ribosome profiling with stalled initiation complexes. MBio 10:e02819-18 http://dx.doi.org/10.1128/mBio.02819-18. [PubMed]
7. Hücker SM, Vanderhaeghen S, Abellan-Schneyder I, Wecko R, Simon S, Scherer S, Neuhaus K. 2018. A novel short l-arginine responsive protein-coding gene ( laoB) antiparallel overlapping to a CadC-like transcriptional regulator in Escherichia coli O157:H7 Sakai originated by overprinting. BMC Evol Biol 18:21 http://dx.doi.org/10.1186/s12862-018-1134-0. [PubMed]
8. Hücker SM, Vanderhaeghen S, Abellan-Schneyder I, Scherer S, Neuhaus K. 2018. The novel anaerobiosis-responsive overlapping gene ano is overlapping antisense to the annotated gene ECs2385 of Escherichia coli O157:H7 Sakai. Front Microbiol 9:931 http://dx.doi.org/10.3389/fmicb.2018.00931. [PubMed]
9. D’Lima NG, Khitun A, Rosenbloom AD, Yuan P, Gassaway BM, Barber KW, Rinehart J, Slavoff SA. 2017. Comparative proteomics enables identification of nonannotated cold shock proteins in E. coli. J Proteome Res 16:3722–3731 http://dx.doi.org/10.1021/acs.jproteome.7b00419. [PubMed]
10. Hemm MR, Paul BJ, Schneider TD, Storz G, Rudd KE. 2008. Small membrane proteins found by comparative genomics and ribosome binding site models. Mol Microbiol 70:1487–1501 http://dx.doi.org/10.1111/j.1365-2958.2008.06495.x. [PubMed]
11. Warren AS, Archuleta J, Feng WC, Setubal JC. 2010. Missing genes in the annotation of prokaryotic genomes. BMC Bioinformatics 11:131 http://dx.doi.org/10.1186/1471-2105-11-131. [PubMed]
12. Müller SA, Kohajda T, Findeiss S, Stadler PF, Washietl S, Kellis M, von Bergen M, Kalkhof S. 2010. Optimization of parameters for coverage of low molecular weight proteins. Anal Bioanal Chem 398:2867–2881 http://dx.doi.org/10.1007/s00216-010-4093-x. [PubMed]
13. DiMaio D. 2014. Viral miniproteins. Annu Rev Microbiol 68:21–43 http://dx.doi.org/10.1146/annurev-micro-091313-103727. [PubMed]
14. Short JD, Pfarr CM. 2002. Translational regulation of the JunD messenger RNA. J Biol Chem 277:32697–32705 http://dx.doi.org/10.1074/jbc.M204553200. [PubMed]
15. Basrai MA, Hieter P, Boeke JD. 1997. Small open reading frames: beautiful needles in the haystack. Genome Res 7:768–771 http://dx.doi.org/10.1101/gr.7.8.768. [PubMed]
16. Impens F, Rolhion N, Radoshevich L, Bécavin C, Duval M, Mellin J, García Del Portillo F, Pucciarelli MG, Williams AH, Cossart P. 2017. N-terminomics identifies Prli42 as a membrane miniprotein conserved in Firmicutes and critical for stressosome activation in Listeria monocytogenes. Nat Microbiol 2:17005 http://dx.doi.org/10.1038/nmicrobiol.2017.5. [PubMed]
17. Ochman H. 2002. Distinguishing the ORFs from the ELFs: short bacterial genes and the annotation of genomes. Trends Genet 18:335–337 http://dx.doi.org/10.1016/S0168-9525(02)02668-9.
18. Storz G, Wolf YI, Ramamurthi KS. 2014. Small proteins can no longer be ignored. Annu Rev Biochem 83:753–777 http://dx.doi.org/10.1146/annurev-biochem-070611-102400. [PubMed]
19. Samayoa J, Yildiz FH, Karplus K. 2011. Identification of prokaryotic small proteins using a comparative genomic approach. Bioinformatics 27:1765–1771 http://dx.doi.org/10.1093/bioinformatics/btr275. [PubMed]
20. Goli B, Nair AS. 2012. The elusive short gene: an ensemble method for recognition for prokaryotic genome. Biochem Biophys Res Commun 422:36–41 http://dx.doi.org/10.1016/j.bbrc.2012.04.090. [PubMed]
21. Wood DE, Lin H, Levy-Moonshine A, Swaminathan R, Chang YC, Anton BP, Osmani L, Steffen M, Kasif S, Salzberg SL. 2012. Thousands of missed genes found in bacterial genomes and their analysis with COMBREX. Biol Direct 7:37 http://dx.doi.org/10.1186/1745-6150-7-37. [PubMed]
22. Óhéigeartaigh SS, Armisén D, Byrne KP, Wolfe KH. 2014. SearchDOGS bacteria, software that provides automated identification of potentially missed genes in annotated bacterial genomes. J Bacteriol 196:2030–2042 http://dx.doi.org/10.1128/JB.01368-13. [PubMed]
23. Hemm MR, Paul BJ, Miranda-Ríos J, Zhang A, Soltanzad N, Storz G. 2010. Small stress response proteins in Escherichia coli: proteins missed by classical proteomic studies. J Bacteriol 192:46–58 http://dx.doi.org/10.1128/JB.00872-09. [PubMed]
24. VanOrsdel CE, Kelly JP, Burke BN, Lein CD, Oufiero CE, Sanchez JF, Wimmers LE, Hearn DJ, Abuikhdair FJ, Barnhart KR, Duley ML, Ernst SEG, Kenerson BA, Serafin AJ, Hemm MR. 2018. Identifying new small proteins in Escherichia coli. Proteomics 18:e1700064 http://dx.doi.org/10.1002/pmic.201700064. [PubMed]
25. Meydan S, Marks J, Klepacki D, Sharma V, Baranov PV, Firth AE, Margus T, Kefi A, Vázquez-Laslop N, Mankin AS. 2019. Retapamulin-assisted ribosome profiling reveals the alternative bacterial proteome. Mol Cell 74:481–493.e6 http://dx.doi.org/10.1016/j.molcel.2019.02.017. [PubMed]
26. Guan Z, Wang X, Raetz CR. 2011. Identification of a chloroform-soluble membrane miniprotein in Escherichia coli and its homolog in Salmonella typhimurium. Anal Biochem 409:284–289 http://dx.doi.org/10.1016/j.ab.2010.10.035. [PubMed]
27. Miravet-Verde S, Ferrar T, Espadas-García G, Mazzolini R, Gharrab A, Sabido E, Serrano L, Lluch-Senar M. 2019. Unraveling the hidden universe of small proteins in bacterial genomes. Mol Syst Biol 15:e8290 http://dx.doi.org/10.15252/msb.20188290. [PubMed]
28. Yuan P, D’Lima NG, Slavoff SA. 2018. Comparative membrane proteomics reveals a nonannotated E. coli heat shock protein. Biochemistry 57:56–60 http://dx.doi.org/10.1021/acs.biochem.7b00864. [PubMed]
29. Reim DF, Speicher DW. 1994. A method for high-performance sequence analysis using polyvinylidene difluoride membranes with a biphasic reaction column sequencer. Anal Biochem 216:213–222 http://dx.doi.org/10.1006/abio.1994.1027. [PubMed]
30. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J. 2003. Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol 21:566–569 http://dx.doi.org/10.1038/nbt810. [PubMed]
31. Kramer G, Sprenger RR, Nessen MA, Roseboom W, Speijer D, de Jong L, de Mattos MJ, Back J, de Koster CG. 2010. Proteome-wide alterations in Escherichia coli translation rates upon anaerobiosis. Mol Cell Proteomics 9:2508–2516 http://dx.doi.org/10.1074/mcp.M110.001826.
32. Van Damme P, Van Damme J, Demol H, Staes A, Vandekerckhove J, Gevaert K. 2009. A review of COFRADIC techniques targeting protein N-terminal acetylation. BMC Proc 3(Suppl 6) :S6 http://dx.doi.org/10.1186/1753-6561-3-s6-s6. [PubMed]
33. Wadler CS, Vanderpool CK. 2007. A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide. Proc Natl Acad Sci USA 104:20454–20459 http://dx.doi.org/10.1073/pnas.0708102104. [PubMed]
34. Park H, McGibbon LC, Potts AH, Yakhnin H, Romeo T, Babitzke P. 2017. Translational repression of the RpoS antiadapter IraD by CsrA is mediated via translational coupling to a short upstream open reading frame. MBio 8:e01355-17 http://dx.doi.org/10.1128/mBio.01355-17. [PubMed]
35. Vecerek B, Moll I, Bläsi U. 2007. Control of Fur synthesis by the non-coding RNA RyhB and iron-responsive decoding. EMBO J 26:965–975 http://dx.doi.org/10.1038/sj.emboj.7601553. [PubMed]
36. Fontaine F, Fuchs RT, Storz G. 2011. Membrane localization of small proteins in Escherichia coli. J Biol Chem 286:32464–32474 http://dx.doi.org/10.1074/jbc.M111.245696. [PubMed]
37. Baek J, Lee J, Yoon K, Lee H. 2017. Identification of unannotated small genes in Salmonella. G3 (Bethesda) 7:983–989 http://dx.doi.org/10.1534/g3.116.036939.
38. Bomjan R, Zhang M, Zhou D. 2019. YshB promotes intracellular replication and is required for Salmonella virulence. J Bacteriol 201:00314–00319 http://dx.doi.org/10.1128/JB.00314-19. [PubMed]
39. Neuhaus K, Landstorfer R, Fellner L, Simon S, Schafferhans A, Goldberg T, Marx H, Ozoline ON, Rost B, Kuster B, Keim DA, Scherer S. 2016. Translatomics combined with transcriptomics and proteomics reveals novel functional, recently evolved orphan genes in Escherichia coli O157:H7 (EHEC). BMC Genomics 17:133 http://dx.doi.org/10.1186/s12864-016-2456-1. [PubMed]
40. Hildebrand PW, Preissner R, Frömmel C. 2004. Structural features of transmembrane helices. FEBS Lett 559:145–151 http://dx.doi.org/10.1016/S0014-5793(04)00061-4.
41. Alix E, Blanc-Potard AB. 2009. Hydrophobic peptides: novel regulators within bacterial membrane. Mol Microbiol 72:5–11 http://dx.doi.org/10.1111/j.1365-2958.2009.06626.x. [PubMed]
42. Kolter R, Yanofsky C. 1982. Attenuation in amino acid biosynthetic operons. Annu Rev Genet 16:113–134 http://dx.doi.org/10.1146/annurev.ge.16.120182.000553. [PubMed]
43. Ivanov IP, Atkins JF, Michael AJ. 2010. A profusion of upstream open reading frame mechanisms in polyamine-responsive translational regulation. Nucleic Acids Res 38:353–359 http://dx.doi.org/10.1093/nar/gkp1037. [PubMed]
44. Ben-Zvi T, Pushkarev A, Seri H, Elgrably-Weiss M, Papenfort K, Altuvia S. 2019. mRNA dynamics and alternative conformations adopted under low and high arginine concentrations control polyamine biosynthesis in Salmonella. PLoS Genet 15:e1007646 http://dx.doi.org/10.1371/journal.pgen.1007646. [PubMed]
45. Herrero Del Valle A, Seip B, Cervera-Marzal I, Sacheau G, Seefeldt AC, Innis CA. 2020. Ornithine capture by a translating ribosome controls bacterial polyamine synthesis. Nat Microbiol 5:554–561 http://dx.doi.org/10.1038/s41564-020-0669-1. [PubMed]
46. Chadani Y, Niwa T, Izumi T, Sugata N, Nagao A, Suzuki T, Chiba S, Ito K, Taguchi H. 2017. Intrinsic ribosome destabilization underlies translation and provides an organism with a strategy of environmental sensing. Mol Cell 68:528–539.e5 http://dx.doi.org/10.1016/j.molcel.2017.10.020. [PubMed]
47. Levin HL, Schachman HK. 1985. Regulation of aspartate transcarbamoylase synthesis in Escherichia coli: analysis of deletion mutations in the promoter region of the pyrBI operon. Proc Natl Acad Sci USA 82:4643–4647 http://dx.doi.org/10.1073/pnas.82.14.4643. [PubMed]
48. Matsumoto Y, Shigesada K, Hirano M, Imai M. 1986. Autogenous regulation of the gene for transcription termination factor rho in Escherichia coli: localization and function of its attenuators. J Bacteriol 166:945–958 http://dx.doi.org/10.1128/JB.166.3.945-958.1986. [PubMed]
49. Allen RJ, Brenner EP, VanOrsdel CE, Hobson JJ, Hearn DJ, Hemm MR. 2014. Conservation analysis of the CydX protein yields insights into small protein identification and evolution. BMC Genomics 15:946 http://dx.doi.org/10.1186/1471-2164-15-946. [PubMed]
50. Hobson JJ, Gallegos AS, Atha BW III, Kelly JP, Lein CD, VanOrsdel CE, Weldon JE, Hemm MR. 2018. Investigation of amino acid specificity in the CydX small protein shows sequence plasticity at the functional level. PLoS One 13:e0198699 http://dx.doi.org/10.1371/journal.pone.0198699. [PubMed]
51. Hobbs EC, Astarita JL, Storz G. 2010. Small RNAs and small proteins involved in resistance to cell envelope stress and acid shock in Escherichia coli: analysis of a bar-coded mutant collection. J Bacteriol 192:59–67 http://dx.doi.org/10.1128/JB.00873-09. [PubMed]
52. Fozo EM, Hemm MR, Storz G. 2008. Small toxic proteins and the antisense RNAs that repress them. Microbiol Mol Biol Rev 72:579–589 http://dx.doi.org/10.1128/MMBR.00025-08. [PubMed]
53. Fozo EM, Kawano M, Fontaine F, Kaya Y, Mendieta KS, Jones KL, Ocampo A, Rudd KE, Storz G. 2008. Repression of small toxic protein synthesis by the Sib and OhsC small RNAs. Mol Microbiol 70:1076–1093 http://dx.doi.org/10.1111/j.1365-2958.2008.06394.x. [PubMed]
54. Pedersen K, Gerdes K. 1999. Multiple hok genes on the chromosome of Escherichia coli. Mol Microbiol 32:1090–1102 http://dx.doi.org/10.1046/j.1365-2958.1999.01431.x. [PubMed]
55. Wilmaerts D, Bayoumi M, Dewachter L, Knapen W, Mika JT, Hofkens J, Dedecker P, Maglia G, Verstraeten N, Michiels J. 2018. The persistence-inducing toxin HokB forms dynamic pores that cause ATP leakage. MBio 9:e00744-18 http://dx.doi.org/10.1128/mBio.00744-18. [PubMed]
56. Wilmaerts D, Dewachter L, De Loose PJ, Bollen C, Verstraeten N, Michiels J. 2019. HokB monomerization and membrane repolarization control persister awakening. Mol Cell 75:1031–1042.e4 http://dx.doi.org/10.1016/j.molcel.2019.06.015. [PubMed]
57. Dörr T, Vulić M, Lewis K. 2010. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol 8:e1000317 http://dx.doi.org/10.1371/journal.pbio.1000317. [PubMed]
58. Kim Y, Wood TK. 2010. Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli. Biochem Biophys Res Commun 391:209–213 http://dx.doi.org/10.1016/j.bbrc.2009.11.033. [PubMed]
59. Bishop RE, Leskiw BK, Hodges RS, Kay CM, Weiner JH. 1998. The entericidin locus of Escherichia coli and its implications for programmed bacterial cell death. J Mol Biol 280:583–596 http://dx.doi.org/10.1006/jmbi.1998.1894. [PubMed]
60. VanOrsdel CE, Bhatt S, Allen RJ, Brenner EP, Hobson JJ, Jamil A, Haynes BM, Genson AM, Hemm MR. 2013. The Escherichia coli CydX protein is a member of the CydAB cytochrome bd oxidase complex and is required for cytochrome bd oxidase activity. J Bacteriol 195:3640–3650 http://dx.doi.org/10.1128/JB.00324-13. [PubMed]
61. Wada A, Sako T. 1987. Primary structures of and genes for new ribosomal proteins A and B in Escherichia coli. J Biochem 101:817–820 http://dx.doi.org/10.1093/jb/101.3.817. [PubMed]
62. Panagiotidis CA, Canellakis ES. 1984. Comparison of the basic Escherichia coli antizyme 1 and antizyme 2 with the ribosomal proteins S20/L26 and L34. J Biol Chem 259:15025–15027.
63. Wada A. 1986. Analysis of Escherichia coli ribosomal proteins by an improved two dimensional gel electrophoresis. II. Characterization of four new proteins. J Biochem 100:1595–1605 http://dx.doi.org/10.1093/oxfordjournals.jbchem.a121867. [PubMed]
64. Izutsu K, Wada C, Komine Y, Sako T, Ueguchi C, Nakura S, Wada A. 2001. Escherichia coli ribosome-associated protein SRA, whose copy number increases during stationary phase. J Bacteriol 183:2765–2773 http://dx.doi.org/10.1128/JB.183.9.2765-2773.2001. [PubMed]
65. Natori Y, Nanamiya H, Akanuma G, Kosono S, Kudo T, Ochi K, Kawamura F. 2007. A fail-safe system for the ribosome under zinc-limiting conditions in Bacillus subtilis. Mol Microbiol 63:294–307 http://dx.doi.org/10.1111/j.1365-2958.2006.05513.x. [PubMed]
66. Salazar ME, Podgornaia AI, Laub MT. 2016. The small membrane protein MgrB regulates PhoQ bifunctionality to control PhoP target gene expression dynamics. Mol Microbiol 102:430–445 http://dx.doi.org/10.1111/mmi.13471. [PubMed]
67. Lippa AM, Goulian M. 2009. Feedback inhibition in the PhoQ/PhoP signaling system by a membrane peptide. PLoS Genet 5:e1000788 http://dx.doi.org/10.1371/journal.pgen.1000788. [PubMed]
68. Hobbs EC, Yin X, Paul BJ, Astarita JL, Storz G. 2012. Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance. Proc Natl Acad Sci USA 109:16696–16701 http://dx.doi.org/10.1073/pnas.1210093109. [PubMed]
69. Huang CS, Pedersen BP, Stokes DL. 2017. Crystal structure of the potassium-importing KdpFABC membrane complex. Nature 546:681–685 http://dx.doi.org/10.1038/nature22970. [PubMed]
70. Gassel M, Möllenkamp T, Puppe W, Altendorf K. 1999. The KdpF subunit is part of the K( +)-translocating Kdp complex of Escherichia coli and is responsible for stabilization of the complex in vitro. J Biol Chem 274:37901–37907 http://dx.doi.org/10.1074/jbc.274.53.37901.
71. Wang H, Yin X, Wu Orr M, Dambach M, Curtis R, Storz G. 2017. Increasing intracellular magnesium levels with the 31-amino acid MgtS protein. Proc Natl Acad Sci USA 114:5689–5694 http://dx.doi.org/10.1073/pnas.1703415114. [PubMed]
72. Yin X, Wu Orr M, Wang H, Hobbs EC, Shabalina SA, Storz G. 2019. The small protein MgtS and small RNA MgrR modulate the PitA phosphate symporter to boost intracellular magnesium levels. Mol Microbiol 111:131–144 http://dx.doi.org/10.1111/mmi.14143. [PubMed]
73. Lloyd CR, Park S, Fei J, Vanderpool CK. 2017. The small protein SgrT controls transport activity of the glucose-specific phosphotransferase system. J Bacteriol 199:e00869–e00816 http://dx.doi.org/10.1128/JB.00869-16. [PubMed]
74. Waters LS, Sandoval M, Storz G. 2011. The Escherichia coli MntR miniregulon includes genes encoding a small protein and an efflux pump required for manganese homeostasis. J Bacteriol 193:5887–5897 http://dx.doi.org/10.1128/JB.05872-11. [PubMed]
75. Martin JE, Waters LS, Storz G, Imlay JA. 2015. The Escherichia coli small protein MntS and exporter MntP optimize the intracellular concentration of manganese. PLoS Genet 11:e1004977 http://dx.doi.org/10.1371/journal.pgen.1004977. [PubMed]
76. Miller MJ, Gennis RB. 1983. The purification and characterization of the cytochrome d terminal oxidase complex of the Escherichia coli aerobic respiratory chain. J Biol Chem 258:9159–9165.
77. Muller MM, Webster RE. 1997. Characterization of the tol-pal and cyd region of Escherichia coli K-12: transcript analysis and identification of two new proteins encoded by the cyd operon. J Bacteriol 179:2077–2080 http://dx.doi.org/10.1128/JB.179.6.2077-2080.1997. [PubMed]
78. Sun YH, de Jong MF, den Hartigh AB, Roux CM, Rolán HG, Tsolis RM. 2012. The small protein CydX is required for function of cytochrome bd oxidase in Brucella abortus. Front Cell Infect Microbiol 2:47 http://dx.doi.org/10.3389/fcimb.2012.00047. [PubMed]
79. Hoeser J, Hong S, Gehmann G, Gennis RB, Friedrich T. 2014. Subunit CydX of Escherichia coli cytochrome bd ubiquinol oxidase is essential for assembly and stability of the di-heme active site. FEBS Lett 588:1537–1541 http://dx.doi.org/10.1016/j.febslet.2014.03.036. [PubMed]
80. Safarian S, Hahn A, Mills DJ, Radloff M, Eisinger ML, Nikolaev A, Meier-Credo J, Melin F, Miyoshi H, Gennis RB, Sakamoto J, Langer JD, Hellwig P, Kühlbrandt W, Michel H. 2019. Active site rearrangement and structural divergence in prokaryotic respiratory oxidases. Science 366:100–104 http://dx.doi.org/10.1126/science.aay0967. [PubMed]
81. Theßeling A, Rasmussen T, Burschel S, Wohlwend D, Kägi J, Müller R, Böttcher B, Friedrich T. 2019. Homologous bd oxidases share the same architecture but differ in mechanism. Nat Commun 10:5138 http://dx.doi.org/10.1038/s41467-019-13122-4. [PubMed]
82. Duc KM, Kang BG, Lee C, Park HJ, Park YM, Joung YH, Bang IS. 2020. The small protein CydX is required for cytochrome bd quinol oxidase stability and function in Salmonella Typhimurium: a phenotypic study. J Bacteriol 202:00348-18. [PubMed]
83. Safarian S, Rajendran C, Müller H, Preu J, Langer JD, Ovchinnikov S, Hirose T, Kusumoto T, Sakamoto J, Michel H. 2016. Structure of a bd oxidase indicates similar mechanisms for membrane-integrated oxygen reductases. Science 352:583–586 http://dx.doi.org/10.1126/science.aaf2477. [PubMed]
84. Du D, Wang Z, James NR, Voss JE, Klimont E, Ohene-Agyei T, Venter H, Chiu W, Luisi BF. 2014. Structure of the AcrAB-TolC multidrug efflux pump. Nature 509:512–515 http://dx.doi.org/10.1038/nature13205. [PubMed]
85. Stock C, Hielkema L, Tascón I, Wunnicke D, Oostergetel GT, Azkargorta M, Paulino C, Hänelt I. 2018. Cryo-EM structures of KdpFABC suggest a K + transport mechanism via two inter-subunit half-channels. Nat Commun 9:4971 http://dx.doi.org/10.1038/s41467-018-07319-2. [PubMed]
86. Nakahigashi K, Takai Y, Kimura M, Abe N, Nakayashiki T, Shiwa Y, Yoshikawa H, Wanner BL, Ishihama Y, Mori H. 2016. Comprehensive identification of translation start sites by tetracycline-inhibited ribosome profiling. DNA Res 23:193–201 http://dx.doi.org/10.1093/dnares/dsw008. [PubMed]
87. Canchaya C, Fournous G, Chibani-Chennoufi S, Dillmann ML, Brüssow H. 2003. Phage as agents of lateral gene transfer. Curr Opin Microbiol 6:417–424 http://dx.doi.org/10.1016/S1369-5274(03)00086-9.
88. Lerat E, Ochman H. 2005. Recognizing the pseudogenes in bacterial genomes. Nucleic Acids Res 33:3125–3132 http://dx.doi.org/10.1093/nar/gki631. [PubMed]
89. Orr MW, Mao Y, Storz G, Qian SB. 2020. Alternative ORFs and small ORFs: shedding light on the dark proteome. Nucleic Acids Res 48:1029–1042 http://dx.doi.org/10.1093/nar/gkz734. [PubMed]
90. Kawano M, Reynolds AA, Miranda-Rios J, Storz G. 2005. Detection of 5′- and 3′-UTR-derived small RNAs and cis-encoded antisense RNAs in Escherichia coli. Nucleic Acids Res 33:1040–1050 http://dx.doi.org/10.1093/nar/gki256. [PubMed]
91. Hansen FG, Hansen EB, Atlung T. 1982. The nucleotide sequence of the dnaA gene promoter and of the adjacent rpmH gene, coding for the ribosomal protein L34, of Escherichia coli. EMBO J 1:1043–1048 http://dx.doi.org/10.1002/j.1460-2075.1982.tb01294.x. [PubMed]
92. Karp PD, Ong WK, Paley S, Billington R, Caspi R, Fulcher C, Kothari A, Krummenacker M, Latendresse M, Midford PE, Subhraveti P, Gama-Castro S, Muñiz-Rascado L, Bonavides-Martinez C, Santos-Zavaleta A, Mackie A, Collado-Vides J, Keseler IM, Paulsen I. 2018. The EcoCyc database. Ecosal Plus 8: http://dx.doi.org/10.1128/ecosalplus.ESP-0006-2018. [PubMed]
93. Schneider TD, Stephens RM. 1990. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18:6097–6100 http://dx.doi.org/10.1093/nar/18.20.6097. [PubMed]
94. Mann M, Wright PR, Backofen R. 2017. IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions. Nucleic Acids Res 45(W1) :W435–W439 http://dx.doi.org/10.1093/nar/gkx279. [PubMed]
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/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0031-2019
2020-05-08
2021-01-15

Abstract:

was one of the first species to have its genome sequenced and remains one of the best-characterized model organisms. Thus, it is perhaps surprising that recent studies have shown that a substantial number of genes have been overlooked. Genes encoding more than 140 small proteins, defined as those containing 50 or fewer amino acids, have been identified in in the past 10 years, and there is substantial evidence indicating that many more remain to be discovered. This review covers the methods that have been successful in identifying small proteins and the short open reading frames that encode them. The small proteins that have been functionally characterized to date in this model organism are also discussed. It is hoped that the review, along with the associated databases of known as well as predicted but undetected small proteins, will aid in and provide a roadmap for the continued identification and characterization of these proteins in as well as other bacteria.

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Small Proteome
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Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019
/content/ecosalplus/10.1128/ecosalplus.ESP-0031-2019.fig1
Figure 1
(A) Histogram of currently annotated protein-coding genes in compared to those identified in 2013. (B) Histogram of currently annotated small protein genes in compared to those known in 2013. For both (A) and (B), the light gray bars represent small protein genes annotated in 2013, and the dark gray bars represent genes annotated in 2019. Data on annotated genes in 2013 are from K12 MG1655 genome annotation U00096.2. Data on annotated genes in 2019 were compiled from a combination of annotations from EcoCyc ( 92 ) and recent papers identifying new small proteins.
ecosalplus/9/1/ESP-0031-2019_fig_001_thmb.gif
ecosalplus/9/1/ESP-0031-2019_fig_001.gif
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Figure 1

(A) Histogram of currently annotated protein-coding genes in compared to those identified in 2013. (B) Histogram of currently annotated small protein genes in compared to those known in 2013. For both (A) and (B), the light gray bars represent small protein genes annotated in 2013, and the dark gray bars represent genes annotated in 2019. Data on annotated genes in 2013 are from K12 MG1655 genome annotation U00096.2. Data on annotated genes in 2019 were compiled from a combination of annotations from EcoCyc ( 92 ) and recent papers identifying new small proteins.

Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019
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Figure 2
The sequence logo for ribosome binding sites is reproduced from reference 93 . Sequences of 12 small protein genes of unknown function are listed below. Red type corresponds to the predicted start codon, while the blue type indicates stretches of four or more G and A residues. Gibbs free energies (ΔG° in kcal/mol) for the interaction between the sequence shown and the 16S RNA were calculated using IntaRNA (http://rna.informatik.uni-freiburg.de/IntaRNA/Input.jsp) ( 94 ). No value is given for the three sequences for which no significant interaction was detected. Rpm (reads per million mapped) values for ribosome profiling carried out in the presence of the inhibitor Onc112 are taken from reference 6 .
ecosalplus/9/1/ESP-0031-2019_fig_002_thmb.gif
ecosalplus/9/1/ESP-0031-2019_fig_002.gif
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Figure 2

The sequence logo for ribosome binding sites is reproduced from reference 93 . Sequences of 12 small protein genes of unknown function are listed below. Red type corresponds to the predicted start codon, while the blue type indicates stretches of four or more G and A residues. Gibbs free energies (ΔG° in kcal/mol) for the interaction between the sequence shown and the 16S RNA were calculated using IntaRNA (http://rna.informatik.uni-freiburg.de/IntaRNA/Input.jsp) ( 94 ). No value is given for the three sequences for which no significant interaction was detected. Rpm (reads per million mapped) values for ribosome profiling carried out in the presence of the inhibitor Onc112 are taken from reference 6 .

Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019
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Figure 3
Structures of AcrZ, KdpF, CydX, and CydH (red) in association with the AcrB multidrug efflux pump (PDB 4C48 [ 84 ]), Kdp potassium transporter (PDB 5MRW [ 69 ]), and cytochrome oxidase (PDB 6RKO [ 80 ]), respectively. The approximate position of the membrane is indicated by shading.
ecosalplus/9/1/ESP-0031-2019_fig_003_thmb.gif
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Figure 3

Structures of AcrZ, KdpF, CydX, and CydH (red) in association with the AcrB multidrug efflux pump (PDB 4C48 [ 84 ]), Kdp potassium transporter (PDB 5MRW [ 69 ]), and cytochrome oxidase (PDB 6RKO [ 80 ]), respectively. The approximate position of the membrane is indicated by shading.

Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019
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Tables

Small Proteome
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Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019
/content/ecosalplus/10.1128/ecosalplus.ESP-0031-2019.T1
Table 1
Overview of known small protein functions
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Table 1

Overview of known small protein functions

Citation: Hemm M, Weaver J, Storz G. 2020. Small Proteome, EcoSal Plus 2020; doi:10.1128/ecosalplus.ESP-0031-2019

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