9B03
INF2 in the Middle of F-Actin (Up state)
Summary for 9B03
| Entry DOI | 10.2210/pdb9b03/pdb |
| EMDB information | 44026 |
| Descriptor | Actin, alpha skeletal muscle, Inverted formin-2, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | actin, formin, filament, severing, cytosolic protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 350488.80 |
| Authors | Palmer, N.J.,Barrie, K.R.,Dominguez, R. (deposition date: 2024-03-11, 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 Cited by 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: 38843827DOI: 10.1038/s41586-024-07637-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.95 Å) |
Structure validation
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