Crystal Structure of a Designed Tetratricopeptide Repeat Module in Complex with its Peptide Ligand

Journal Article · Fri Jan 01 04:00:00 EST 2010 · FEBS Journal

DOI:https://doi.org/10.1111/j.1742-4658.2009.07549.x· OSTI ID:1019583

Cortajarena, A; Wang, J; Regan, L

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1019583
• Report Number(s): BNL--95428-2011-JA
• Journal Information: FEBS Journal, Journal Name: FEBS Journal Journal Issue: 4 Vol. 277; ISSN 1742-464X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
CRYSTAL STRUCTURE
DESIGN
IN VIVO
PEPTIDES
PROTEINS
RESIDUES
national synchrotron light source