Dataset Information

Intermolecular Architecture of Fibrin Clots and its Interaction INterface with Albumin

ABSTRACT: In this project we establish the unit cell of fibrin polymer network by using of XL-MS methods and modelling approaches. With shotgun proteomics approach we estimate the ratio of proteins in the purified Fibrin Clots and ratio of Albumin inter- and intralinks

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Oleg Klykov

LAB HEAD: Albert J. R. Heck

PROVIDER: PXD011680 | Pride | 2020-01-09

REPOSITORIES: Pride

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Publications

Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling.

Klykov Oleg O van der Zwaan Carmen C Heck Albert J R AJR Meijer Alexander B AB Scheltema Richard A RA

Proceedings of the National Academy of Sciences of the United States of America 20200110 4

Upon activation, fibrinogen forms large fibrin biopolymers that coalesce into clots which assist in wound healing. Limited insights into their molecular architecture, due to the sheer size and the insoluble character of fibrin clots, have restricted our ability to develop novel treatments for clotting diseases. The, so far resolved, disparate structural details have provided insights into linear elongation; however, molecular details like the C-terminal domain of the α-chain, the heparin-binding ...[more]

PMID: 31924745

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Project description:Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis. The unfavorable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported both in thrombotic APS and venous thromboembolism (VTE). The presence and amount of different proteins within a plasma clot, not only associated with the coagulation system, may influence clot properties. To our knowledge, there is a lack of data on plasma fibrin-clot bound proteins in patients with thrombotic APS or VTE. The aim of our study was to perform a quantitative proteomic analysis of fibrin clots prepared from citrated plasma from subjects with thrombotic APS and prior VTE, along with fibrin clot permeability (Ks) and clot lysis time (CLT) assessed ex vivo. We investigated 23 consecutive patients with APS, 18 with a history of first-ever VTE, and 20 age and sex matched healthy subjects. A multiple enzyme digestion filter aided sample preparation and a multienzyme digestion (MED) FASP method combined with LC-MS/MS analysis performed on a Proxeon Easy-nLC System coupled to the Q Exactive HF mass spectrometer were used. The proteomic analysis revealed that clot composition regarding 117 proteins in APS patients and 48 proteins in VTE patients was changed as compared to healthy controls, while 72 clot-bounded proteins differed between APS and VTE subjects. In healthy controls, Ks was associated with fibrinogen alpha and gamma chains (r=0.46 and r=0.46, both p<0.05, respectively) or apolipoprotein B-100 (r=-0.53, p<0.05), while CLT correlated with annexin A2 (r=-0.58, p<0.05), apolipoportein(a) (r=0.47, p<0.05), or platelet glycoprotein 4 (r=0.59, p<0.05). In VTE patients correlations of Ks with complement C1q and histone H2B, as factors closely linked with thrombosis, were observed (r=-0.52 and r=-0.47, both p<0.05, respectively). In patients with thrombotic APS all above-mentioned associations were not found. This study is the first to show that different proteins are able to influence the clot formation, structure, and properties. Since, prothrombotic conditions abolished associations observed in healthy subjects fibrin clots, differences in protein clot components might explain the links between prothrombotic fibrin clot phenotype and thromboembolic events.

Dataset Information

Intermolecular Architecture of Fibrin Clots and its Interaction INterface with Albumin

Publications

Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling.

Similar Datasets

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