纤溶酶
克林格尔域
化学
丝氨酸蛋白酶
尿激酶
蛋白酶
纤维蛋白
生物化学
劈理(地质)
受体
蛋白质结构
细胞生物学
生物物理学
酶
生物
免疫学
遗传学
古生物学
断裂(地质)
作者
Ruby H. P. Law,Tom T. Caradoc-Davies,Nathan Cowieson,Anita J. Horvath,Adam J. Quek,Joanna Amarante Encarnacao,David L. Steer,Angus D. Cowan,Qingwei Zhang,Bernadine G.C. Lu,Robert N. Pike,A. Ian Smith,Paul Coughlin,James C. Whisstock
出处
期刊:Cell Reports
[Elsevier]
日期:2012-03-01
卷期号:1 (3): 185-190
被引量:204
标识
DOI:10.1016/j.celrep.2012.02.012
摘要
Plasminogen is the proenzyme precursor of the primary fibrinolytic protease plasmin. Circulating plasminogen, which comprises a Pan-apple (PAp) domain, five kringle domains (KR1-5), and a serine protease (SP) domain, adopts a closed, activation-resistant conformation. The kringle domains mediate interactions with fibrin clots and cell-surface receptors. These interactions trigger plasminogen to adopt an open form that can be cleaved and converted to plasmin by tissue-type and urokinase-type plasminogen activators. Here, the structure of closed plasminogen reveals that the PAp and SP domains, together with chloride ions, maintain the closed conformation through interactions with the kringle array. Differences in glycosylation alter the position of KR3, although in all structures the loop cleaved by plasminogen activators is inaccessible. The ligand-binding site of KR1 is exposed and likely governs proenzyme recruitment to targets. Furthermore, analysis of our structure suggests that KR5 peeling away from the PAp domain may initiate plasminogen conformational change.
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