4AU3

Crystal Structure of a Hsp47-collagen complex

Summary for 4AU3

• Entry DOI: 10.2210/pdb4au3/pdb
• Related: 4AWR
• Descriptor: SERPIN PEPTIDASE INHIBITOR, CLADE H (HEAT SHOCK PROTEIN 47 ), MEMBER 1, (COLLAGEN BINDING PROTEIN 1), SERPYIN PEPTIDASE INHIBITOR, CLADE H (HEAT SHOCK PROTEIN 47 ), MEMBER 1, (COLLAGEN BINDING PROTEIN 1), 18ER COLLAGEN MODEL PEPTIDE 15-R8 (3 entities in total)
• Functional Keywords: chaperone-peptide complex, chaperone, chaperone/peptide
• Biological source: CANIS LUPUS FAMILIARIS (DOG); More
• Cellular location: Secreted, extracellular space, extracellular matrix: E2RHY7
• Total number of polymer chains: 10
• Total formula weight: 189248.20

Authors

Widmer, C.,Gebauer, J.M.,Brunstein, E.,Rodenbaum, S.,Zaucke, F.,Drogemuller, C.,Leeb, T.,Baumann, U. (deposition date: 2012-05-14, release date: 2012-08-15, Last modification date: 2024-10-23)

Primary citation

Widmer, C.,Gebauer, J.M.,Brunstein, E.,Rosenbaum, S.,Zaucke, F.,Drogemuller, C.,Leeb, T.,Baumann, U.
Molecular Basis for the Action of the Collagen-Specific Chaperone Hsp47/Serpinh1 and its Structure-Specific Client Recognition.
Proc.Natl.Acad.Sci.USA, 109:13243-, 2012

PubMed Abstract: Collagen is the most abundant protein in animals and is a major component of the extracellular matrix in tissues such as skin and bone. A distinctive structural feature of all collagen types is a unique triple-helical structure formed by tandem repeats of the consensus sequence Xaa-Yaa-Gly, in which Xaa and Yaa frequently are proline and hydroxyproline, respectively. Hsp47/SERPINH1 is a procollagen-specific molecular chaperone that, unlike other chaperones, specifically recognizes the folded conformation of its client. Reduced functional levels of Hsp47 were reported in severe recessive forms of osteogenesis imperfecta, and homozygous knockout is lethal in mice. Here we present crystal structures of Hsp47 in its free form and in complex with homotrimeric synthetic collagen model peptides, each comprising one Hsp47-binding site represented by an arginine at the Yaa-position of a Xaa-Yaa-Gly triplet. Two of these three binding sites in the triple helix are occupied by Hsp47 molecules, which bind in a head-to-head fashion, thus making extensive contacts with the leading and trailing strands of the collagen triple helix. The important arginine residue within the Xaa-Arg-Gly triplet is recognized by a conserved aspartic acid. The structures explain the stabilization of the triple helix as well as the inhibition of collagen-bundle formation by Hsp47. In addition, we propose a pH-dependent substrate release mechanism based on a cluster of histidine residues.

PubMed: 22847422
DOI: 10.1073/PNAS.1208072109

Experimental method

X-RAY DIFFRACTION (2.78 Å)