Structure of Human J-type Co-chaperone HscB Reveals a Tetracysteine Metal-binding Domain

Iron-sulfur proteins play indispensable roles in a broad range of biochemical processes. The biogenesis of iron-sulfur proteins is a complex process that has become a subject of extensive research. The final step of iron-sulfur protein assembly involves transfer of an iron-sulfur cluster from a clus...

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Published inThe Journal of biological chemistry Vol. 283; no. 44; pp. 30184 - 30192
Main Authors Bitto, Eduard, Bingman, Craig A., Bittova, Lenka, Kondrashov, Dmitry A., Bannen, Ryan M., Fox, Brian G., Markley, John L., Phillips, George N.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 31.10.2008
American Society for Biochemistry and Molecular Biology
Subjects
Amino Acid Sequence
ANIMALS
BACTERIA
Binding Sites
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
Crystallography, X-Ray - methods
CRYSTALS
Cysteine - chemistry
ESCHERICHIA COLI
Heat-Shock Proteins - chemistry
HUMAN POPULATIONS
Humans
Iron-Sulfur Proteins - chemistry
MATERIALS SCIENCE
METALS
Metals - chemistry
Mitochondria - metabolism
Molecular Chaperones - chemistry
Molecular Conformation
Molecular Sequence Data
NORMAL-MODE ANALYSIS
PLANTS
Protein Structure and Folding
Protein Structure, Tertiary
PROTEINS
RUBREDOXIN
Rubredoxins - chemistry
Sequence Homology, Amino Acid
ZINC
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Summary:Iron-sulfur proteins play indispensable roles in a broad range of biochemical processes. The biogenesis of iron-sulfur proteins is a complex process that has become a subject of extensive research. The final step of iron-sulfur protein assembly involves transfer of an iron-sulfur cluster from a cluster-donor to a cluster-acceptor protein. This process is facilitated by a specialized chaperone system, which consists of a molecular chaperone from the Hsc70 family and a co-chaperone of the J-domain family. The 3.0Å crystal structure of a human mitochondrial J-type co-chaperone HscB revealed an L-shaped protein that resembles Escherichia coli HscB. The important difference between the two homologs is the presence of an auxiliary metal-binding domain at the N terminus of human HscB that coordinates a metal via the tetracysteine consensus motif CWXCX9–13FCXXCXXXQ. The domain is found in HscB homologs from animals and plants as well as in magnetotactic bacteria. The metal-binding site of the domain is structurally similar to that of rubredoxin and several zinc finger proteins containing rubredoxin-like knuckles. The normal mode analysis of HscB revealed that this L-shaped protein preferentially undergoes a scissors-like motion that correlates well with the conformational changes of human HscB observed in the crystals.
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USDOE
The atomic coordinates and structure factors (code 3bvo) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
This work was supported, in whole or in part, by National Institutes of Health Grants P50 GM64598 and U54 GM074901 (to J. L. M.). This work was also supported by the Department of Energy, Basic Energy Sciences, Office of Science, under Contract W-31-109-ENG-38, by National Cancer Institute Grant Y1-CO-1020, and by National Institute of General Medical Science Grant Y1-GM-1104. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry, University of Wisconsin, Madison, WI 53706. Tel.: 608-263-6142; Fax: 608-263-6142; E-mail: phillips@biochem.wisc.edu.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Movies S1–S3.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M804746200