Substrate-induced remodeling of the active site regulates human HTRA1 activity

Nat Struct Mol Biol. 2011 Mar;18(3):386-8. doi: 10.1038/nsmb.2013. Epub 2011 Feb 6.

Abstract

Crystal structures of active and inactive conformations of the human serine protease HTRA1 reveal that substrate binding to the active site is sufficient to stimulate proteolytic activity. HTRA1 attaches to liposomes, digests misfolded proteins into defined fragments and undergoes substrate-mediated oligomer conversion. In contrast to those of other serine proteases, the PDZ domain of HTRA1 is dispensable for activation or lipid attachment, indicative of different underlying mechanistic features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • High-Temperature Requirement A Serine Peptidase 1
  • Humans
  • Hydrolysis
  • Models, Molecular
  • PDZ Domains
  • Protein Binding
  • Protein Folding
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*

Substances

  • High-Temperature Requirement A Serine Peptidase 1
  • HtrA1 protein, human
  • Serine Endopeptidases