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Crystal structure and mutational analysis of a functionally intact bovine hsc70
Author(s) -
Jiang Jianwen,
Prasad Kondury,
Lafer Eileen Marilyn,
Sousa Rui
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a962-a
Subject(s) - linker , atp hydrolysis , atpase , chaperone (clinical) , chemistry , biophysics , crystallography , protein folding , allosteric regulation , protein domain , biology , biochemistry , enzyme , medicine , pathology , computer science , gene , operating system
Hsp70 proteins are highly conserved molecular chaperones that are widely involved in protein folding, protein degradation, protein complex remodeling, protein translocation, and some other cellular processes. Hsp70s are comprised of an N‐terminal ATPase domain and a C‐terminal protein substrate binding domain (SBD). Cycles of ATP binding and hydrolysis in the ATPase domain are allosterically coupled to substrate binding and release in the SBD. The structure of an Hsp70 with both domains has not previously been determined, so the mechanism of interdomain communication has remained obscure. We have determined the crystal structures of a functionally intact bovine Hsc70 chaperone at 2.6 Å resolution. Mutational analysis of the Hsc70 interdomain interface and interdomain linker confirms that interdomain communication occurs across the interface seen in the crystal and also involves the adjacent interdomain linker. Upon ATP binding, this hydrophobic linker appears to become buried in the interdomain interface where it may displace interdomain interactions and force the two domains to move relatively each other to relieve steric clashes created by the linker's intrusion. (This work was supported by grants from NIH GM‐52522 and Welch foundation AQ‐1486 to R.S. and from the Muscular Dystrophy Association MDA3473 and NINDS NS‐29051 to E.M.L.)