2024年6月6日,來自美國賓夕法尼亞大學佩雷爾曼醫學院Roberto Dominguez團隊在《自然》雜志上發表了標題為“Mechanisms of actin filament severing and elongation by formins.”的研究成果,提出了肌動蛋白絲形成素切斷和伸長的機制。










Humans express fifteen formins, playing crucial roles in actin-based processes, such as cytokinesis, cell motility, and mechanotransduction?1,2. However, the lack of structures bound to the actin filament (F-actin) has been a major impediment to understanding formin function. While formins are known for their ability to nucleate and elongate F-actin?3-7, some formins can additionally depolymerize, sever, or bundle F-actin. Two mammalian formins, inverted formin-2 (INF2) and diaphanous-1 (Dia1), exemplify this diversity. INF2 displays potent severing activity but elongates weakly?8-11, whereas Dia1 has potent elongation activity but does not sever?4,8. Using cryo-electron microscopy (cryo-EM), we reveal five structural states of INF2 and two of Dia1 bound to the middle and barbed end of F-actin. INF2 and Dia1 bind differently to these sites, consistent with their distinct activities. The FH2 and WH2 domains of INF2 are positioned to sever F-actin, whereas Dia1 appears unsuited for severing. Structures also show how profilin-actin is delivered to the fast-growing barbed end, and how this is followed by a transition of the incoming monomer into the F-actin conformation and the release of profilin. Combined, the seven structures presented here provide step-by-step visualization of the mechanisms of F-actin severing and elongation by formins.



Palmer, Nicholas J., Barrie, Kyle R. et al,Mechanisms of actin filament severing and elongation by formins.DOI: 10.1038/s41586-024-07637-0, Nature:最新IF:69.504



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