Substrate-induced remodeling of the active site regulates human HTRA1 activity
Substrate-induced remodeling of the active site regulates human HTRA1 activity
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DOI：
10.1038/nsmb.2013
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发表时间：
2011-03-01
影响因子：
16.8
通讯作者：
Ehrmann, Michael
中科院分区：
文献类型：
--
作者：
Truebestein, Linda;Tennstaedt, Annette;Ehrmann, Michael
人丝氨酸蛋白酶HTRA1的活性和非活性构象的晶体结构表明，底物与活性位点的结合足以刺激蛋白水解活性。HTRA1附着在脂质体上，将错误折叠的蛋白质折叠成确定的片段，并进行底物介导的寡聚体转化。与其他丝氨酸蛋白酶相比，HTRA 1的PDZ结构域对于激活或脂质附着是不可或缺的，这表明了不同的潜在机制特征。
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.