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 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 3.0 A 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 CWXCX(9-13)FCXXCXXXQ. 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.
Bitto
Eduard
E
Center for Eukaryotic Structural Genomics, University of Wisconsin-Madison, Madison, Wisconsin 53706-1544, USA.
Bingman
Craig A
CA
Bittova
Lenka
L
Kondrashov
Dmitry A
DA
Bannen
Ryan M
RM
Fox
Brian G
BG
Markley
John L
JL
Phillips
George N
GN
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D003545:Cysteine / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000737:chemistry*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012416:Rubredoxins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
C490651:HSCB protein, human; D006360:Heat-Shock Proteins; D007506:Iron-Sulfur Proteins; D008670:Metals; D018832:Molecular Chaperones; D012416:Rubredoxins; D003545:Cysteine