Trübestein, Linda; Tennstaedt, Annette; Mönig, Timon; Krojer, Tobias; Canellas, Flavia; Kaiser, Markus; Clausen, Tim; Ehrmann, Michael:

Substrate induced remodeling of the active site regulates human HtrA1 activity

In: Nature structural & molecular biology : NSMB, Jg. 18 (2011), S. 386–388
ISSN: 1545-9993
Zeitschriftenaufsatz / Fach: Biologie
Fakultät für Biologie
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.