Molecular dynamics simulation study on the structures of fascin mutants

Abstract

Fascin is a filamentous actin (F-actin) bundling protein, which cross-links F-actin into bundles and becomes an important component of filopodia on the cell surface. Fascin is overexpressed in many types of cancers. The mutation of fascin affects its ability to bind to F-actin and the progress of cancer. In this paper, we have studied the effects of residues of K22, K41, K43, K241, K358, K399, and K471 using molecular dynamics (MD) simulation. For the strong-effect residues, that is, K22, K41, K43, K358, and K471, our results show that the mutation of K to A leads to large values of

A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation

“…FRET analysis of the conformational dynamics of Fascin-1 and fluorescence recovery after photobleaching (FRAP) analysis of the dynamics of Fascin-1 association with actin [ 49 ] suggest that Fascin-1 oscillates between a compact, actin-binding conformation and an open state upon phosphorylation at Ser 39 by PKC ( figure 3 d ). Molecular dynamics simulations of Fascin-1 mutants with impaired actin binding display different conformations and increased protein flexibility compared to WT Fascin-1 [ 50 , 51 ]. Furthermore, Fascin-1-dependent actin-bundling in functional filopodia is not characterized by stable cross-linking of actin fibres, but rather is a highly dynamic process involving rapid cycles of actin binding and disassociation.…”