SH3BGRL proteins are thioredoxin fold-containing actin filament pointed end capping proteins (TPECs).

ABSTRACT: Cellular actin dynamics are tightly regulated by actin-binding proteins with specialized domains. Here, we identify SH3BGRL proteins as modulators of actin dynamics, characterized by their thioredoxin (Trx) fold and the absence of the canonical enzymatic site. The Trx fold is generally associated with enzymatic activity; however, in this context, it functions non-enzymatically to enhance actin nucleation, inhibit depolymerization and cap the growing pointed end of the actin filament. Our results indicate that all SH3BGRL isoforms weakly promote actin nucleation in vitro by stabilizing energetically unstable actin dimers and trimers. Using molecular dynamics simulations and assays that directly probe the pointed end of the actin filament, we show that SH3BGRL proteins efficiently inhibit ac

SUBMITTER: Heiringhoff RS 

PROVIDER: S-EPMC12827327 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature