Chapter 6 : Temperature-Dependent Molecular Adaptation Features in Proteins

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Temperature-Dependent Molecular Adaptation Features in Proteins, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815813/9781555814229_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555815813/9781555814229_Chap06-2.gif


This chapter compares and reviews the molecular adaptations shown by thermophilic and psychrophilic proteins. At both high and low temperatures, the proteins need to be active to maintain the cellular machinery in functional state. The proteins appear to achieve this by modulating their conformational stability/flexibility. The overall fold appears to remain conserved among the homologous thermophilic, mesophilic, and psychrophilic proteins, and only rather minor adjustments are required for adaptation of the protein to high and low temperatures. Thermophilic proteins have specific amino acid composition requirements. In general, thermophilic proteins favor charged residues (Glu, Arg, and Lys) capable of providing increased formation of the ion pairs and their networks. Surface loops in the thermophilic proteins may be undesirable due to the increased mobility at high temperatures. Psychrophilic proteins have high specific activities, yet their thermal stabilities are relatively low. Psychrophilic proteins are often more flexible, particularly, in the regions near the active sites. That proteins could adapt to the diverse living temperatures of their source organisms by modulating the electrostatic effects came to light from studies on citrate synthase.

Citation: Kumar S, Arya S, Nussinov R. 2007. Temperature-Dependent Molecular Adaptation Features in Proteins, p 75-85. In Gerday C, Glansdorff N (ed), Physiology and Biochemistry of Extremophiles. ASM Press, Washington, DC. doi: 10.1128/9781555815813.ch6
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Adams, M., W. W., and, R. M. Kelly. 1995. Enzymes from microorganisms in extreme environments. Chem. Engng. News 73: 3242.
2. Alsop, E.,, M. Silver, and, D. R. Livesay. 2003. Optimized electrostatic surfaces parallel increased thermostability: a structural bioinformatics analysis. Protein Eng. 16: 871874.
3. Arnorsdottir, J.,, M. M. Kristjansson, and, R. Ficnor. 2005. Crystal structure of a subtilisin-like serine proteinase from a psychrotrophic Vibrio species reveals structural aspects of cold adaptation. FEBS J. 272: 832845.
4. Arya, S. 2005. Phyletic and comparative statistical analysis of protein sequences as well as structures from the extremophilic bacteria. M.Tech. Thesis. Indian Institute of Technology, Kanpur, UP, India.
5. Bae, E.,, and G. N. Phillips, Jr. 2004. Structures and analysis of highly homologous psychrophilic, mesophilic, and thermophilic adenylate kinases. J. Biol. Chem. 279: 2820228208.
6. Baker, P. J. 2004. From hyperthermophiles to psychrophiles: the structural basis of temperature stability of the amino acid dehydrogenases. Biochem. Soc. Trans. 32: 264268.
7. Baskakov, I.,, and D. W. Bolen. 1998. Forcing thermodynamically unfolded proteins to fold. J. Biol. Chem. 273: 48314834.
8. Bastolla, U.,, A. Moya,, E. Viguera, and, R. C. van Ham. 2004. Genomic determinants of protein folding thermodynamics in prokaryotic organisms. J. Mol. Biol. 343: 14511466.
9. Berman, H. M.,, J. Westbrook,, Z. Feng,, G. Gilliland,, T. N. Bhat,, H. Weissig,, I. N. Shindyalov, and, P. E. Bourne. 2000. The Protein Data Bank. Nucleic Acids Res. 28: 235242.
10. Bjork, A.,, D. Mantzilas,, R. Sirevag, and, V. G. Eijsink. 2003. Electrostatic interactions across the dimer–dimer interface contribute to the pH-dependent stability of a tetrameric malate dehydrogenase. FEBS Lett. 553: 423426.
11. Blochl, E.,, R. Rachel,, S. Burggraf,, D. Hafenbradl,, H. W. Jannasch, and, K. O. Stetter. 1997. Pyrolobus fumarii, gen. and sp. nov., represents a novel group of archaea, extending the upper temperature limit for life to 113 degrees C. Extremophiles 1: 1421.
12. Brandsdal, B. O.,, E. S. Heimstad,, I. Sylte, and, A. O. Smalas. 1999. Comparative molecular dynamics of mesophilic and psychrophilic protein homologues studied by 1.2 ns simulations. J. Biomol. Struct. Dyn. 17: 493506.
13. Bosshard, H. R.,, D. N. Marti, and, I. Jelesarov. 2004. Protein stabilization by salt bridges: concepts, experimental approaches and clarification of some misunderstandings. J. Molec. Recog. 17: 116.
14. Butterwick, J. A.,, J. P. Loria,, N. S. Astrof,, C. D. Kroenke,, R. Cole,, M. Rance, and, A. G. Palmer III. 2004. Multiple time scale backbone dynamics of homologous thermophilic and mesophilic ribonuclease HI enzymes. J. Mol. Biol. 339: 855871.
15. Cavicchioli, R.,, and K. S. Siddiqui. 2004. Cold adapted enzymes, p. 615–638. In A. Pandey,, C. Webb,, C. R. Soccol, and, C. Larroche (ed.), Enzyme Technology. AsiaTech Publishers Inc., New Delhi, India.
16. Cavicchioli, R.,, K. S. Siddiqui,, D. Andrews, and, K. R. Sowers. 2002. Low-temperature extremophiles and their applications. Curr. Opin. Biotechnol. 13: 253261.
17. Chakravarty, S.,, and R. Varadarajan. 2002. Elucidation of factors responsible for enhanced thermal stability of proteins: a structural genomics based study. Biochemistry 41: 81528161.
18. Chan, C. H.,, H. K. Liang,, N. W. Hsiao,, M. T. Ko,, P. C. Lyu, and, J. K. Hwang. 2004. Relationship between local structural entropy and protein thermostability. Proteins: Struct. Funct. Bioinfo. 57: 684691.
19. Claverie, P.,, C. Viganob,, J. M. Ruysschaertb,, C. Gerday, and, G. Feller. 2003. The precursor of a psychrophilic α-amylase: structural characterization and insights into cold adaptation. Biochim. Biophys. Acta 1649: 119122.
20. D’Amico, S.,, C. Gerday, and, G. Feller. 2003a. Temperature adaptation of proteins: Engineering mesophilic-like activity and stability in a cold adapted alpha-amylase. J. Mol. Biol. 332: 981988.
21. D’Amico, S.,, J. C. Marx,, C. Gerday, and, G. Feller. 2003b. Activity–stability relationships in extremophilic enzymes. J. Biol. Chem. 278: 78917896.
22. Dalhus, B.,, M. Saarinen,, U. H. Sauer,, P. Eklund,, K. Johansson,, A. Karlsson,, S. Ramaswamy,, A. Bjork,, B., Synstad,, K. Naterstad,, R. Sirevag, and, H. Eklund. 2002. Structural basis of thermophilic protein stability: Structures of thermophilic and mesophilic malate dehydrogenases. J. Mol. Biol. 318: 707721.
23. De Farias, S. T.,, and M. C. Bonato. 2002. Preferred codons and amino acid couples in hyperthermophiles. Genome Biol. 3: Preprint.
24. Deming, J. W. 2002. Psychrophiles and polar regions. Curr. Opin. Micrbiol. 5: 301309.
25. Dominy, B. N.,, H. Minoux, and, C. L. Brooks III. 2004. An electrostatic basis for the stability of thermophilic proteins. Proteins 57: 128141.
26. Dong, F.,, and H. X. Zhou. 2002. Electrostatic contributions to T4 lysozyme stability: solvent-exposed charges versus semi-buried salt bridges. Biophys. J. 83: 13411347.
27. Dunker, A. K.,, J. D. Lawson,, C. J. Brown,, R. M. Williams,, P. Romero,, J. S. Oh,, C. J. Oldfield,, A. M. Campen,, C. M. Ratliff,, K. W. Hipps,, J. Ausio,, M. S. Nissen,, R. Reeves,, C. Kang,, C. R. Kissinger,, R. W. Bailey,, M. D. Griswold,, W. Chiu,, E. C. Garner, and, Z. Obradovic. 2001. Intrinsically disordered protein. J. Mol. Graph. Model. 19: 2659.
28. Dunker, A. K.,, C. J. Brown,, J. D. Lawson,, L. M. Iakoucheva, and, Z. Obradovic. 2002. Intrinsic disorder and protein function. Biochemistry 41: 65736582.
29. Dyson, H. J.,, and P. E. Wright. 2005. Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6: 197208.
30. Eijsink, V., G. H.,, A. Bjork,, S. Gaseidnes,, R. Sirevag,, B. Synstad,, B. van den Burg, and, G. Vriend. 2004. Rational engineering of enzyme stability. J. Biotechnol. 113: 105120.
31. Elcock, A. H. 1998. The stability of salt bridges at high temperatures: Implications for hyperthermophilic proteins. J. Mol. Biol. 284: 489502.
32. Feller, G. 2003. Molecular adaptations to cold in psychrophilic enzymes. Cell. Mol. Life Sci. 60: 648662.
33. Feller, G.,, and C. Gerday. 2003. Psychrophilic enzymes: Hot topics in cold adaptation. Nat. Rev. Microbiol. 1: 200208.
34. Fitzpatrick, T. B.,, P. Killer,, R. M. Thomas,, I. Jelesarov,, N. Amrhein, and, P. Macheroux. 2001. Chorismate synthase from the hyperthermophile Thermotoga maritima combines thermostability and increased rigidity with catalytic and spectral properties similar to mesophilic Counterparts. J. Biol. Chem. 276: 1805218059.
35. Friedman, R.,, J. W. Drake, and, A. L. Hughes. 2004. Genome-wide patterns of nucleotide substitution reveal stringent functional constraints on the protein sequences of thermophiles. Genetics 167: 15071512.
36. Fukuchi, S.,, and K. Nishikawa. 2001. Protein surface amino acid compositions distinctively differ between thermophilic and mesophilic Bacteria. J. Mol. Biol. 309: 835843.
37. Garofoli, S.,, M. Falconi, and, A. Desideri. 2004. Thermostability of wild type and mutant cold shock proteins by molecular dynamics simulation. J. Biomol. Struct. Dyn. 21: 771779.
38. Georlette, D.,, V. Blaise,, T. Collins,, S. D’Amico,, E. Gratia,, A. Hoyoux,, J. C. Marx,, G. Sonan,, G. Feller, and, C. Gerday. 2004. Some like it cold: biocatalysis at low temperatures. FEMS Microbiol. Rev. 28: 2542.
39. Gianese, G.,, P. Argos, and, S. Pascarella. 2001. Structural adaptation of enzymes to low temperatures. Protein Eng. 14: 141148.
40. Glansdorff, N. 1999. On the origin of operons and their possible role in evolution towards thermophily. J. Mol. Evol. 49: 432438.
41. Gorfe, A. A.,, B. O. Brandsdal,, H. K. Leiros,, R. Helland, and, A. O. Smalas. 2000. Electrostatics of mesophilic and psychrophilic trypsin isoenzymes: qualitative evaluation of electrostatic differences at the substrate binding site. Proteins: Struct. Funct. Bioinfo. 40: 207217.
42. Gromiha, M. M.,, S. Thomas, and, C. Santhosh. 2002. Role of cation–pi interactions to the stability of thermophilic proteins. Prep. Biochem. Biotechnol. 32: 355362.
43. Gruia, A. D.,, S. Fischer, and, J. C. Smith. 2003. Molecular dynamics simulation reveals a surface salt bridge forming a kinetic trap in unfolding of truncated Staphylococcal nuclease. Proteins: Struct. Funct. Bioinfo. 50: 507515.
44. Gunasekaran, K.,, C. J. Tsai,, S. Kumar,, D. Zanuy, and, R. Nussinov. 2003. Extended disordered proteins: targeting function with less scaffold. Trends Biochem. Sci. 28: 8185.
45. Hendsch, Z. S.,, and B. Tidor. 1994. Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci. 3: 211226.
46. Ibrahim, B. S.,, and V. Pattabhi. 2004. Role of weak interactions in thermal stability of proteins. Biochem. Biophys. Res. Commun. 325: 10821089.
47. Jaenicke, R. 2000. Do ultrastable proteins from hyperthermophiles have high or low conformational rigidity? Proc. Natl. Acad. Sci. USA 97: 29622964.
48. Kajander, T.,, P. C. Kahn,, S. H. Passila,, D. C. Cohen,, L. Lehtio,, W. Adolfsen,, J. Warwicker,, U. Schell, and, A. Goldman. 2000. Buried charged surface in proteins. Structure 8: 12031214.
49. Karshikoff, A.,, and R. Ladenstein. 2001. Ion pairs and the thermo-tolerance of proteins from hyperthermophiles: a “traffic rule” for hot roads. Trends Biochem. Sci. 26: 550556.
50. Karshikoff, A.,, and R. Ladenstein. 1998. Proteins from thermophilic and mesophilic organisms essentially do not differ in packing. Protein Eng. 11: 867- 872.
51. Kim, S. Y.,, K. Y. Hwang,, S. H. Kim,, H. C. Sung,, Y. S. Han, and, Y. Cho. 1999. Structural basis for cold adaptation: sequence, biochemical properties, and crystal structure of malate dehydrogenase from a psychrophilic Aquaspirillum arcticum. J. Biol. Chem. 274: 1176111767.
52. Kleiger G., R., Grothe, P. Mallick, and, D. Eisenberg. 2002. GXXXG and AXXXA: common alpha-helical interaction motifs in proteins, particularly in extremophiles. Biochemistry 41: 59905997.
53. Kumar, S.,, and R. Nussinov. 2004a. Different roles of electrostatics in heat and in cold: adaptation by citrate synthase. ChemBioChem. 5: 280290.
54. Kumar, S.,, and R. Nussinov. 2004b. Experiment-guided thermodynamic simulations on reversible two-state proteins: implications for protein thermostability. Biophys. Chem. 111: 235246.
55. Kumar, S.,, C. J. Tsai, and, R. Nussinov. 2003. Temperature range of thermodynamic stability for the native state of reversible two-state proteins. Biochemistry 42: 48644873.
56. Kumar, S.,, and R. Nussinov. 2001a. How do thermophilic proteins deal with heat? Cell. Mol. Life Sci. 58: 12161233.
57. Kumar, S.,, and R. Nussinov. 2001b. Fluctuations in ion pairs and their stabilities in proteins. Proteins: Struct. Funct. Genet. 43: 433454.
58. Kumar, S.,, C. J. Tsai, and, R. Nussinov. 2001. Thermodynamic differences among homologous thermophilic and mesophilic proteins. Biochemistry 40: 1415214165.
59. Kumar, S.,, C. J. Tsai, and, R. Nussinov. 2000a. Factors enhancing protein thermostability. Protein Eng. 13: 179191.
60. Kumar, S.,, B. Ma,, C. J. Tsai, and, R. Nussinov. 2000b. Electrostatic strengths of salt bridges in thermophilic and mesophilic gluta-mate dehydrogenase monomers. Proteins: Struct. Funct. Genet. 38: 368383.
61. Kumar, S.,, and R. Nussinov. 1999. Salt bridge stability in monomeric proteins. J. Mol. Biol. 293: 12411255.
62. Liang, H. K.,, C. M. Huang,, M. T. Ko, and, J. K. Hwang. 2005. Amino acid coupling patterns in thermophilic proteins. Proteins: Struct. Funct. Bioinfo. 59: 5863.
63. Lebbink, J. H.,, V. Consalvi,, R. Chiaraluce,, K. D. Berndt, and, R. Ladenstein. 2002. Structural and thermodynamic studies on a salt-bridge triad in the NADP-binding domain of glutamate dehydrogenase from Thermotoga maritima: Cooperativity and electrostatic contribution to stability. Biochemistry 41: 1552415535.
64. Lee, C. F.,, M. D. Allen,, M. Bycroft, and, K. B. Wong. 2005. Electrostatic interactions contribute to reduced heat capacity change of unfolding in a thermophilic ribosomal protein L30e. J. Mol. Biol. 348: 419431.
65. Loladze, V. V.,, and G. I. Makhatadze. 2005. Both helical propensity and side chain hydrophobicity at a partially exposed site in alpha-helix contribute to the thermodynamic stability of Ubiquitin. Proteins: Struct. Funct. Bioinfo. 58: 16.
66. Makhatadze, G. I.,, V. V. Loladze,, D. N. Ermolenko,, X. Chen, and, S. T. Thomas. 2003. Contribution of surface salt bridges to protein stability: guidelines for protein engineering. J. Mol. Biol. 327: 11351148.
67. Mallick, P.,, D. R. Boutz,, D. Eisenberg, and, T. O. Yeates. 2002. Genomic evidence that the intracellular proteins of archaeal microbes contain disulfide bonds. Proc. Natl. Acad. Sci. USA 99: 96799684.
68. Marti, D. N.,, and H. R. Bosshard. 2003. Electrostatic interactions in leucine zippers: thermodynamic analysis of the contributions of Glu and His residues and the effect of mutating salt bridges. J. Mol. Biol. 330: 621637.
69. Marx, J. C.,, V. Blaise,, T. Collins,, S. D’Amico,, D. Delille,, E. Gratia,, A. Hoyoux,, A. L. Huston,, G. Sonan,, G. Feller, and, C. Gerday. 2004. A perspective on cold enzymes: current knowledge and frequently asked questions. Cell. Mol. Biol. 50: 643655.
70. Mavromatis, K.,, I. Tsigos,, M. Tzanodaskalaki,, M. Kokkinidis, and, V. Bouriotis. 2002. Exploring the role of a glycine cluster in cold adaptation of an alkaline phosphatase. Eur. J. Biochem. 269: 23302335.
71. Mozo-Villarias, A.,, J. Cedano, and, E. Querol. 2003. A simple electrostatic criterion for predicting the thermal stability of proteins. Protein Eng. 16: 279286.
72. Mueller, U.,, D. Perl,, F. X. Schmid, and, U. Heinemann. 2000. Thermal stability and atomic-resolution crystal structure of the Bacillus caldolyticus cold shock protein. J. Mol. Biol. 297: 975988.
73. Nakashima, H.,, S. Fukuchi, and, K. Nishikawa. 2003. Compositional changes in RNA, DNA and proteins for bacterial adaptation to higher and lower temperatures. J. Biochem (Tokyo) 133: 507513.
74. Nordberg, K. E.,, S. J. Crennell,, C. Higgins,, S. Nawaz,, L. Yeoh,, D. W. Hough, and, M. J. Danson. 2003. Citrate synthase from Thermus aquaticus: a thermostable bacterial enzyme with a five-membered inter-subunit ionic network. Extremophiles 7: 916.
75. Ogasahara, K.,, M. Ishida, and, K. Yutani. 2003. Stimulated interaction between α and β subunits of tryptophan synthase from hyperthermophile enhances its stability. J. Biol. Chem. 278: 89228928.
76. Pack, S. P.,, and Y. J. Yoo. 2005. Packing-based difference of structural features between thermophilic and mesophilic proteins. Int. J. Biol. Macromol. 35: 169174.
77. Perl, D.,, C. Welker,, T. Schindler,, K. Schroder,, M. A. Marahiel,, R. Jaenicke, and, F. X. Schmid. 1998. Conservation of rapid two-state folding in mesophilic, thermophilic and hyperthermophilic cold shock proteins. Nat. Struct. Biol. 5: 229235.
78. Perl, D.,, U. Mueller,, U. Heinemann, and, F. X. Schmid. 2000. Two exposed amino acid residues confer thermostability on a cold shock protein. Nat. Struct. Biol. 7: 380383.
79. Robinson-Rechavi, M.,, and A. Godzik. 2005. Structural genomics of Thermotoga maritima proteins shows that contact order is a major determinant of protein thermostability. Structure 13: 857860.
80. Robinson-Rechavi, M.,, A. Alibes, and, A. Godzik. 2006. Contribution of electrostatic interactions, compactness and quaternary structure to protein thermostability: Lessons from structural genomics of Thermotoga maritima. J. Mol. Biol. 356: 547557.
81. Romero, P.,, Z. Obradovic,, X. Li,, E. C. Garner,, C. J. Brown, and, A. K. Dunker. 2001. Sequence complexity of disordered protein. Proteins: Struct. Funct. Genet. 42: 3848.
82. Russell, N. J. 2000. Toward a molecular understanding of cold activity of enzymes from psychrophiles. Extremophiles 4: 8390.
83. Russell, R. J.,, U. Gerike,, M. J. Danson,, D. W. Hough, and, G. L. Taylor. 1998. Structural adaptations of the cold-active citrate synthase from an Antarctic bacterium. Structure 6: 351361.
84. Schneider, D.,, Y. Liu,, M. Gerstein,, D. M. Engelman. 2002. Thermostability of membrane protein helix–helix interaction elucidated by statistical analysis. FEBS Lett. 532: 231236.
85. Sens, S.,, and J. W. Peters. 2006. The thermal adaptation of the nitrogenase Fe protein from thermophilic Methanobacter thermoautotrophicus. Proteins: Struct. Funct. Bioinfo. 62: 450460.
86. Siddiqui, K. S.,, A. Poljak,, M. Guilhaus,, D. de Fancisci,, P. M. G. Curmi,, G. Feller,, S. D’Amico,, C. Gerday,, V. N. Uversky, and, R. Cavicchioli. 2006. The role of lysine versus arginine in enzyme cold-adaptation: Modifying lysine to homo-arginine stabilized the cold-adapted α-amylase from Psuedoalteramonas haloplanktis. Proteins: Struct. Funct. Bioinf, 64: 486501.
87. Simonson, T.,, J. Carlsson, and, D. A. Case. 2004. Proton binding to proteins: pk a calculations with explicit and implicit solvent models. J. Am. Chem. Soc. 126: 41674180.
88. Sterner, R.,, and W. Liebl. 2001. Thermophilic adaptation of proteins. Crit. Rev. Biochem. Mol. Biol. 36: 39106.
89. Taka, J.,, K. Ogasahara,, J. Jeyakanthan,, N. Kunishima,, C. Kuroishi,, M. Sugahara,, S. Yokoyama, and, K. Yutani. 2005. Stabilization due to dimer formation of phosphoribsyl anthrani-late isomerase from Thermus thermophilus HB8: X-ray analysis and DSC experiments. J. Biochem. 137: 569578.
90. Tindbaek, N.,, A. Svendsen,, P. R. Oestergaard, and, H. Draborg. 2004. Engineering a substrate specific cold adapted subtilisin. Protein Eng. Des. Sel. 17: 149156.
91. Thomas, A. S.,, and A. H. Elcock. 2004. Molecular simulations suggest protein salt bridges are uniquely suited to life at high temperatures. J. Am. Chem. Soc. 126: 22082214.
92. Thompson, M. J.,, and D. Eisenberg. 1999. Transproteomic evidence of a loop-deletion mechanism for enhancing protein thermostability. J. Mol. Biol. 290: 595604.
93. Torrez, M.,, M. Schultehenrich, and, D. R. Livesay. 2003. Conferring thermostability to mesophilic proteins through optimized electrostatic surfaces. Biophys. J. 85: 28452853.
94. Uversky, V. N.,, C. J. Oldfield, and, A. K. Dunker. 2005. Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling. J. Mol. Recognit. 18: 343384.
95. Wales, D. J.,, and P. E. Dewsbury. 2004. Effect of salt bridges on the energy landscape of a model protein. J. Chem. Phys. 121: 1028410290.
96. Wright, P. E.,, and H. J. Dyson. 1999. Intrinsically unstructured proteins: re-assessing the protein structure–function paradigm. J. Mol. Biol. 293: 321331.
97. Zhang, J. H.,, L. L. Zhang, and, L. X. Zhou. 2004. Thermostability of protein studied by molecular dynamics simulation. J. Biomol. Struct. Dyn. 21: 657662.
98. Zhou, H. X. 2002. Towards the physical basis of thermophilic proteins: linking of enriched polar interactions and reduced heat capacity of unfolding. Biophys. J. 83: 31263133.
99. Zhou, H. X.,, and F. Dong. 2003. Electrostatic contributions to the stability of a thermophilic cold shock protein. Biophys. J. 84: 22162222.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error