Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
AI Summary:
Fascin-1-mediated actin-bundling activity is central to the generation of plasma membrane protrusions required for cell migration. The identification of Nb 3E11, a nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation, could aid in the development of Fascin-1 targeted therapeutics.AI Topics:
Fascin-1-mediated actin-bundling activity is central to the generation of plasma membrane protrusions required for cell migration. Dysregulated formation of cellular protrusions is observed in metastatic cancers, where they are required for increased invasiveness, and is often correlated with increased Fascin-1 abundance. 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 and filopodia formation. 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 β-trefoil domain of Fascin-1 that is currently not targeted by chemical inhibitors. Binding of Nb 3E11 to Fascin-1 induces a conformational change in the adjacent domains to stabilize Fascin-1 in an inhibitory state similar to that adopted in the presence of small-molecule inhibitors. Nb 3E11 could be used as a tool inhibitor molecule to aid in the development of Fascin-1 targeted therapeutics.
Burgess, Selena G.
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listPaul, Nikki R.
Author
Nikolaou, Savvas and Juin, Amelie and Whitelaw, Jamie A. and Paul, Nikki R. and Fort, Loic and Nixon, Colin and Spence, Heather J. and Bryson, Sheila and Machesky, Laura M. (2024) CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. eLife, 13: e83712. ISSN 2050-084X
Mandrou, Elena and Thomason, Peter A. and Paschke, Peggy I. and Paul, Nikki R. and Tweedy, Luke and Insall, Robert (2024) A reliable system for quantitative g-protein activation imaging in cancer cells. Cells, 13 (13): 1114. ISSN 2073-4409
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listRichards, Mark W.
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listAult, James R.
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listAskenatzis, Laurie
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listClaydon, Sophie G.
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listCorbyn, Ryan
Author
Xavier, Vanessa and Martinelli, Silvia and Corbyn, Ryan and Pennie, Rachel and Rakovic, Kai and Powley, Ian R. and Officer-Jones, Leah and Ruscica, Vincenzo and Galloway, Alison and Carlin, Leo M. and Cowling, Victoria H. and Le Quesne, John and Martinou, Jean-Claude and MacVicar, Thomas (2024) Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression. Life Science Alliance, 7 (11): e202402764. ISSN 2575-1077
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listMachesky, Laura M.
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
See full publications listBayliss, Richard
Author
Burgess, Selena G. and Paul, Nikki R. and Richards, Mark W. and Ault, James R. and Askenatzis, Laurie and Claydon, Sophie G. and Corbyn, Ryan and Machesky, Laura M. and Bayliss, Richard (2024) A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation. Open Biology, 14 (3): 230376. ISSN 2046-2441
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