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-Structure paper
タイトル | Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 11, Page 1774-1785, Year 2023 |
掲載日 | 2023年9月25日 |
著者 | Wout Oosterheert / Florian E C Blanc / Ankit Roy / Alexander Belyy / Micaela Boiero Sanders / Oliver Hofnagel / Gerhard Hummer / Peter Bieling / Stefan Raunser / |
PubMed 要旨 | The release of inorganic phosphate (P) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. The mechanisms underlying P release ...The release of inorganic phosphate (P) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. The mechanisms underlying P 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 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 escapes rapidly from the filament end but slowly from internal subunits. In a nemaline-myopathy-associated actin variant, the backdoor is predominantly open in filament-core subunits, resulting in accelerated P release and filaments with drastically shortened ADP-P caps. Our results provide the molecular basis for P release from actin and exemplify how a disease-linked mutation distorts the nucleotide-state distribution and atomic structure of the filament. |
リンク | Nat Struct Mol Biol / PubMed:37749275 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.28 - 3.59 Å |
構造データ | EMDB-16887, PDB-8oi6: EMDB-16888, PDB-8oi8: EMDB-16889, PDB-8oid: |
化合物 | ChemComp-ADP: ChemComp-MG: ChemComp-HOH: |
由来 |
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キーワード | STRUCTURAL PROTEIN / Actin filament / cytoskeletal protein / ATPase |