title: The X-ray crystal structure of full-length human plasminogen.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, VIC 3800 Australia.
authors: Ruby H P
authors: RH
authors: Law
authors: Tom
authors: T
authors: Caradoc-Davies
authors: Nathan
authors: N
authors: Cowieson
authors: Anita J
authors: AJ
authors: Horvath
authors: Adam J
authors: AJ
authors: Quek
authors: Joanna Amarante
authors: JA
authors: Encarnacao
authors: David
authors: D
authors: Steer
authors: Angus
authors: A
authors: Cowan
authors: Qingwei
authors: Q
authors: Zhang
authors: Bernadine G C
authors: BG
authors: Lu
authors: Robert N
authors: RN
authors: Pike
authors: A Ian
authors: AI
authors: Smith
authors: Paul B
authors: PB
authors: Coughlin
authors: James C
authors: JC
authors: Whisstock
mesh_terms: D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D006031:Glycosylation; D006801:Humans; D018082:Kringles; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010958:Plasminogen / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D010958:Plasminogen