title: Substrate-induced remodeling of the active site regulates human HTRA1 activity.
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.
authors.affiliation: Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Truebestein
authors.forename: Annette
authors.initials: A
authors.lastname: Tennstaedt
authors.forename: Timon
authors.initials: T
authors.lastname: Mönig
authors.forename: Tobias
authors.initials: T
authors.lastname: Krojer
authors.forename: Flavia
authors.initials: F
authors.lastname: Canellas
authors.forename: Markus
authors.initials: M
authors.lastname: Kaiser
authors.forename: Tim
authors.initials: T
authors.lastname: Clausen
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrmann
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D054731:PDZ Domains; D011485:Protein Binding; D017510:Protein Folding; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases