Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments.

ABSTRACT: The release of inorganic phosphate (P_i) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. The mechanisms underlying P_i release from the core and barbed end of actin filaments remain unclear. Here, using human and bovine actin isoforms, we combine cryo-EM with molecular-dynamics simulations and in vitro reconstitution to demonstrate how actin releases P_i through a 'molecular backdoor'. While constantly open at the barbed end, the backdoor is predominantly closed in filament-core subunits and opens only transiently through concerted amino acid rearrangements. This explains why P_i escapes rapidly from the filament end but slowly from internal subunits. In a nemaline-myopathy-ass

SUBMITTER: Oosterheert W 

PROVIDER: S-EPMC10643162 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature