Chapter 12 : Sensing Metals: the Versatility of Fur

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This chapter describes the characteristics and physiological role of each subfamily, the shared and specialized structural features, and the recognition pattern of target binding sites in detail. The level of intracellular iron is regulated by various iron-sensing regulators. Intracellular manganese is reported as abundant as zinc in many bacteria, whereas it is about one-tenth of zinc in . It is known to be sensed by MntR of the DtxR family in , and a Fur family member in α-proteobacteria. In , nickel induces and represses Ni-containing and Fe-containing superoxide dismutases (SODs), respectively. In , nickel induces and represses Ni-containing and Fe-containing SODs, respectively. It was found that one of its four Fur homologs regulates these two SODs in addition to nickel-uptake systems and, hence, was named Nur. The Irr protein was first described in as an iron-responsive regulator of the Fur family that controls genes for heme biosynthesis and iron uptake systems. Binding of more than two Fur dimers may occur in sites with extended footprints, whereas tight binding with only a single dimer to one core motif is possible. The similarity of recognition sequences hinders precise prediction of regulon members based on simple consensus sequences. Structural information of various Fur members will continue to provide insights into how metal specificity is achieved in metalloregulators, providing better ways to design specific metal sensors and to predict functions of uncharacterized metalloproteins.

Citation: Cha S, Shin J, Roe J. 2011. Sensing Metals: the Versatility of Fur, p 191-204. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch12
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Image of Figure 1.
Figure 1.

Diversity of Fur subfamilies. Specialized Fur subfamilies with respect to their activity modulators (specific metals, peroxide, heme, etc.) are presented with representative gene functions they regulate and the mode of regulation. Activity modulators that stimulate and inhibit activities are presented with arrows and bars that are directed toward each Fur subfamily, respectively. Specific metals that confer DNA binding activity to the apo-form (collectively designated as Fur in shaded rectangles) are indicated. The arrows and bars originating from each Fur subfamily toward target gene functions indicate positive and negative regulation modes, respectively. Dotted rectangular boxes around Ni-Nur and Irr/Mn-Mur indicate phylogenetic restrictions to actinobacteria and α-proteobacteria, respectively.

Citation: Cha S, Shin J, Roe J. 2011. Sensing Metals: the Versatility of Fur, p 191-204. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch12
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Image of Figure 2.
Figure 2.

Structure of functionally active form of representative Fur members: Fur from ( Fur) and Nur from ( Nur). Ribbon diagrams of DNA binding-competent Fur (Pohl et al., ) and Nur (An et al., ) are presented along with the contour of binding DNA (dotted circle). Secondary structure elements of DNA binding (DB) domain (H1-H4, S1, S2) and metal sites (M for metal at hinge region, D for metal at dimeric core site, Ni for nickel-specific site) are labeled. Dimeric core region in ScNur is veiled by transparent surface. Reprinted from (An et al., ), with permission of the publisher.

Citation: Cha S, Shin J, Roe J. 2011. Sensing Metals: the Versatility of Fur, p 191-204. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch12
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Image of Figure 3.
Figure 3.

A model for inducing DNA-binding activity of Fur family regulators by binding regulatory metals. (A) Dimeric apo-Fur proteins with only structural metal bindings (at sites 1 and/or 2) assume linear (flung-out) arrangement of DNA-binding (DB) relative to dimeric (D) domains. Binding of regulatory metals in the interdomain region (sites 3 or 4) might produce active spatial arrangement of DB domains to interact with DNA. In DB-incompetent apo-PerR from ( PerR), site 1 (C site consisting of four Cys residues) is occupied by zinc (Traore et al., 2006). In DB-competent structure of Fur from ( Fur) and , sites 2 and 3 are occupied. In active Nur from , sites 3 and 4 are occupied (An et al., ). In inactive Zur from ( Zur), sites 1, 2, and 3 are occupied with low stoichiometric occupancy (Lucarelli et al., ). Coordinating residues in each site are presented to show overall similarity as well as differences. (B) The metal site at hinge region. The M sites located in the interdomain hinge region between DB (S1-S2 sheets) and D (S3-S4 sheets) domains are presented in further detail for Zur, Fur, and Nur.

Citation: Cha S, Shin J, Roe J. 2011. Sensing Metals: the Versatility of Fur, p 191-204. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch12
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Table 1.

Representative prokaryotic metal sensors

Citation: Cha S, Shin J, Roe J. 2011. Sensing Metals: the Versatility of Fur, p 191-204. In Storz G, Hengge R (ed), Bacterial Stress Responses, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816841.ch12

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