PXD034866

PXD034866 is an original dataset announced via ProteomeXchange.

Title	Mechano‐covalent protection 1 of procoagulant factor VIII by von Willebrand factor
Description	von Willebrand factor (VWF) is the protective carrier of procoagulant factor VIII (FVIII) in the shear forces of the circulation, prolonging its half‐life and delivering it to the developing thrombus. VWF∙FVIII complex formation is characterized by catch‐bond behavior in which force first decelerates then accelerates bond dissociation. Patients with mutations in VWF at the FVIII binding site phenocopies hemophilia A and the most common mutations involve cysteine residues of multiple disulfides. Thirteen VWF disulfide bonds at the FVIII binding site exist in formed and unformed states, and binding of FVIII results in partial formation of 12 of the VWF bonds. The VWF∙FVIII bond stiffens in response to force and this property is ablated when VWF disulfide bonds are prevented from forming, resulting in slip‐bond behavior. These findings demonstrate that FVIII binding to VWF involves dynamic changes in the covalent states of several VWF disulfides that are required for productive interaction.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:19.042.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Diego Butera
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-24 08:35:37	ID requested
1	2023-07-20 10:35:12	announced
⏵ 2	2023-11-14 09:02:19	announced	2023-11-14: Updated project metadata.

Butera D, Wang HJ, Woon HG, Zhao YC, Ju LA, Hogg PJ, Mechano-covalent protection of coagulation factor VIII by von Willebrand factor. Blood Adv, 7(10):2117-2128(2023) [pubmed]

submitter keyword: cysteines, factor FVIII, von Willebrand factor,disulphide bonds

Philip John Hogg
contact affiliation	The Centenary Institute, University of Sydney, Camperdown NSW 2050, Australia Charles Perkins Centre, The University of Sydney, Camperdown NSW 2050, Australia.
contact email	phil.hogg@sydney.edu.au
lab head
Diego Butera
contact affiliation	ACRF Centenary Cancer Research Centre
contact email	diegobutera@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD034866

PRIDE project URI

• PRIDE
  1. PXD034866
     1. Label: PRIDE project
     2. Name: Mechano‐covalent protection 1 of procoagulant factor VIII by von Willebrand factor