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

被引：109

作者：

Truebestein, Linda ^{[1
]}

Tennstaedt, Annette ^{[1
]}

Moenig, Timon ^{[2
]}

Krojer, Tobias ^{[3
]}

Canellas, Flavia ^{[3
]}

Kaiser, Markus ^{[2
]}

Clausen, Tim ^{[3
]}

Ehrmann, Michael ^{[1
]}

机构：

[1] Univ Duisburg Essen, Fac Biol, Ctr Med Biotechnol, Essen, Germany

[2] Max Planck Gesell, Chem Genom Ctr, Dortmund, Germany

[3] Research Inst Mol Pathol IMP, Vienna, Austria

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 03期

关键词：

CRYSTAL-STRUCTURE; PROTEASE DOMAIN; SERINE; STRESS; DEGP; PDZ; ACTIVATION; SIGNALS;

D O I：

10.1038/nsmb.2013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：386 / 388

页数：3

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