9B27

Dia1 at the Barbed End of F-Actin

Summary for 9B27

• Entry DOI: 10.2210/pdb9b27/pdb
• EMDB information: 44099
• Descriptor: Actin, alpha skeletal muscle, Protein diaphanous homolog 1, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: actin, filament, elongation, ends, cytosolic protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Total number of polymer chains: 8
• Total formula weight: 349411.41

Authors

Palmer, N.J.,Barrie, K.R.,Dominguez, R. (deposition date: 2024-03-14, release date: 2024-05-29, Last modification date: 2024-08-21)

Primary citation

Palmer, N.J.,Barrie, K.R.,Dominguez, R.
Mechanisms of actin filament severing and elongation by formins.
Nature, 632:437-442, 2024

PubMed Abstract: Humans express fifteen formins, playing crucial roles in actin-based processes, such as cytokinesis, cell motility, and mechanotransduction . 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 , 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 , whereas Dia1 has potent elongation activity but does not sever . 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.

PubMed: 38843827
DOI: 10.1038/s41586-024-07637-0

Experimental method

ELECTRON MICROSCOPY (3.51 Å)