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PMID: 18550409 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structure of the Hsp110:Hsc70 nucleotide exchange machine.

Molecular cell ·Vol. 31 ·No. 2 ·2008-07-25 ·Pages 232-43

Schuermann JP, Jiang J, Cuellar J, Llorca O, Wang L, Gimenez LE, Jin S, Taylor AB, Demeler B, Morano KA, Hart PJ, Valpuesta JM, Lafer EM, Sousa R

Abstract

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of the protein:protein interactions on nucleotide exchange, can be understood in terms of the coupled effects of the nucleotides and protein:protein interactions on the open-closed isomerization of the NBDs. The symmetrical interactions in the complex may model other Hsp70 family heterodimers in which two Hsp70s reciprocally act as NEFs.

MeSH Terms
Animals Cattle Clathrin/metabolism Crystallography, X-Ray Dimerization HSC70 Heat-Shock Proteins/chemistry HSP110 Heat-Shock Proteins/chemistry Humans Hydrogen Bonding Models, Molecular Nucleotides/metabolism Protein Binding Protein Structure, Quaternary Protein Structure, Secondary Protein Structure, Tertiary Saccharomyces cerevisiae/metabolism Solutions
Chemicals
Clathrin HSC70 Heat-Shock Proteins HSP110 Heat-Shock Proteins Nucleotides Solutions
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Schuermann Jonathan P
Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Jiang Jianwen
Cuellar Jorge
Llorca Oscar
Wang Liping
Gimenez Luis E
Jin Suping
Taylor Alexander B
Demeler Borries
Morano Kevin A
Hart P John
Valpuesta Jose M
Lafer Eileen M
Sousa Rui
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2008.05.006
Published
2008-07-25
Epub
2008-00-12
Pages
232-43
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2892728
Subset
IM
Grants
NIA NIH HHS · T32 AG021890 · United States
NINDS NIH HHS · NS029051 · United States
NIA NIH HHS · T32AG021890-03 · United States
PHS HHS · 0755057Y · United States
NIGMS NIH HHS · GM-52522 · United States
NCI NIH HHS · P30 CA054174 · United States
NCI NIH HHS · P30 CA054174-175711 · United States
NINDS NIH HHS · R56 NS029051 · United States
NINDS NIH HHS · R01 NS029051 · United States
NIGMS NIH HHS · R01 GM052522 · United States
NINDS NIH HHS · R01 NS029051-21A1 · United States
NIGMS NIH HHS · R01 GM052522-14 · United States
PHS HHS · AQ-1486 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2008.05.006 PMC Full Text View journal details
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