PXD038713 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A Nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation |
Description | Fascin-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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-03-25 |
AnnouncementXML | Submission_2024-03-25_07:58:35.700.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | James Ault |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Synapt MS |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-12-09 03:30:33 | ID requested | |
⏵ 1 | 2024-03-25 07:58:36 | announced | |
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 affiliation | Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK |
contact email | r.w.bayliss@leeds.ac.uk |
lab head | |
James Ault |
contact affiliation | University of Leeds |
contact email | j.r.ault@leeds.ac.uk |
dataset submitter | |
Full Dataset Link List
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/2024/03/PXD038713 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038713
- Label: PRIDE project
- Name: A Nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation