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PXD038713

PXD038713 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA Nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation
DescriptionFascin-1 mediated actin-bundling activity is central to the generation of plasma membrane protrusions required for cell migration. Dysregulation of cellular protrusions is observed in metastatic cancers, where they are required for increased invasiveness, and this is often correlated with overexpression of Fascin-1. Therefore, there is interest in generating therapeutic Fascin-1 inhibitors. We present the identification of Nb 3E11, a nanobody inhibitor of Fascin-1 actin-bundling activity, filopodia formation and cell migration. The crystal structure of the Fascin-1/Nb 3E11 complex reveals the structural mechanism of inhibition. Nb 3E11 occludes an actin-binding site on the third -trefoil domain of Fascin-1 that is currently untargeted by chemical inhibitors and induces a conformational change in the adjacent domains to stabilise Fascin-1 in an inhibitory state similar to that adopted in the presence of small molecule inhibitors. Nb 3E11 can be utilised as a tool inhibitor molecule to aid in the development of Fascin-1 targeted therapeutics.
HostingRepositoryPRIDE
AnnounceDate2024-03-25
AnnouncementXMLSubmission_2024-03-25_07:58:35.700.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJames Ault
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-12-09 03:30:33ID requested
12024-03-25 07:58:36announced
Publication List
10.1098/rsob.230376;
Burgess SG, Paul NR, Richards MW, Ault JR, Askenatzis L, Claydon SG, Corbyn R, Machesky LM, Bayliss R, A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biol, 14(3):230376(2024) [pubmed]
Keyword List
submitter keyword: fascin-1, hydrogen deuterium exchange,nanobody, hdx
Contact List
Richard W Bayliss
contact affiliationAstbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
contact emailr.w.bayliss@leeds.ac.uk
lab head
James Ault
contact affiliationUniversity of Leeds
contact emailj.r.ault@leeds.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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