Document Detail


Crystal structure of a designed tetratricopeptide repeat module in complex with its peptide ligand.
MedLine Citation:
PMID:  20089039     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tetratricopeptide repeats (TPRs) are protein domains that mediate key protein-protein interactions in cells. Several TPR domains bind the C-termini of the chaperones heat shock protein (Hsp)90 and/or Hsp70, and exchange of such binding partners is key for the heat shock response. We have previously described the design of a TPR protein that binds tightly and specifically to the C-terminus of Hsp90, and in doing so, is able to inhibit chaperone function in vivo. Here we present the X-ray crystal structure of the designed TPR domain (CTPR390) in complex with its peptide ligand--the C-terminal residues of Hsp90 (peptide MEEVD). This structure reveals two interesting aspects of the TPR modules. First, a new packing arrangement of 3-TPR modules is observed. The TPR units stack against each other in an unusual fashion to form infinite superhelices in the crystal. Second, the structure provides insights into the molecular basis of TPR-ligand recognition.
Authors:
Aitziber L Cortajarena; Jimin Wang; Lynne Regan
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Publication Detail:
Type:  Journal Article     Date:  2010-01-18
Journal Detail:
Title:  The FEBS journal     Volume:  277     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-09     Completed Date:  2010-03-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1058-66     Citation Subset:  IM    
Affiliation:
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/3KD7
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MeSH Terms
Descriptor/Qualifier:
Cloning, Molecular
Crystallography, X-Ray
Drug Design
HSP90 Heat-Shock Proteins / metabolism
Ligands
Macromolecular Substances
Models, Molecular*
Peptides / chemistry*,  genetics,  metabolism*
Protein Binding
Protein Structure, Tertiary
Repetitive Sequences, Amino Acid*
Chemical
Reg. No./Substance:
0/HSP90 Heat-Shock Proteins; 0/Ligands; 0/Macromolecular Substances; 0/Peptides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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