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Title | Mechanisms of actin filament severing and elongation by formins. |
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Journal, issue, pages | Nature, Vol. 632, Issue 8024, Page 437-442, Year 2024 |
Publish date | Jun 6, 2024 |
![]() | Nicholas J Palmer / Kyle R Barrie / Roberto Dominguez / ![]() |
PubMed Abstract | Humans express 15 formins that play crucial roles in actin-based processes, including cytokinesis, cell motility and mechanotransduction. However, the lack of structures bound to the actin filament ...Humans express 15 formins that play crucial roles in actin-based processes, including 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. Whereas 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, encoded by DIAPH1), exemplify this diversity. INF2 shows potent severing activity but elongates weakly whereas DIA1 has potent elongation activity but does not sever. Using cryo-electron microscopy (cryo-EM) we show 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 formin-homology 2 and Wiskott-Aldrich syndrome protein-homology 2 (FH2 and WH2, respectively) domains of INF2 are positioned to sever F-actin, whereas DIA1 appears unsuited for severing. These 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. |
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Methods | EM (single particle) |
Resolution | 2.86 - 4.38 Å |
Structure data | ![]() EMDB-44009: INF2 at the Barbed End of F-actin, Consensus refinement ![]() EMDB-44010: INF2 at the Barbed End of F-Actin, Leading WH2 focus refinement ![]() EMDB-44011: INF2 at the Barbed End of F-Actin, Trailing WH2 focus refinement EMDB-44012, PDB-9az4: EMDB-44018, PDB-9azp: EMDB-44019, PDB-9azq: ![]() EMDB-44020: INF2 in the Middle of F-Actin, Up state consensus refinement ![]() EMDB-44022: INF2 in the Middle of F-actin, Up state focus refinement for the static WH2 ![]() EMDB-44023: INF2 in the Middle of Actin filament ![]() EMDB-44024: INF2 at the Middle of F-Actin, Up state mobile FH2 local refinement ![]() EMDB-44025: INF2 in the Middle of Actin Filament, Up state local refinement for static FH2 EMDB-44026, PDB-9b03: ![]() EMDB-44027: INF2 in the middle of F-actin, Down state consensus map ![]() EMDB-44031: INF2 in the Middle of an Actin Filament, Down state actin local refinement ![]() EMDB-44032: INF2 in the Middle of Actin Filament, Down state mobile FH2 local refinement ![]() EMDB-44033: INF2 in the Middle of F-Actin, Down state static FH2 local refinement EMDB-44045, PDB-9b0k: EMDB-44099, PDB-9b27: EMDB-44135: Dia1 in the Middle of F-actin ![]() EMDB-44943: INF2 in the middle of F-Actin, Focus refinement for mobile WH2 ![]() EMDB-44948: INF2 in the Middle of F-actin, Up state mobile WH2 focus refinement ![]() EMDB-44950: INF2 at the Barbed End of F-Actin, Local refinement for actin ![]() EMDB-44951: INF2 at the Barbed End of F-Actin, Leading FH2 focused refinement ![]() EMDB-44956: INF2 at the Barbed END with Incoming Profilin-Actin, Consensus refinement ![]() EMDB-44958: INF2 at the Barbed End of F-Actin with Incoming Profilin-Actin, Actin local refinement ![]() EMDB-44972: INF2 at the Barbed End of F-Actin with Incoming Actin, Actin local refinement ![]() EMDB-44973: INF2 at the Barbed End of F-Actin with Incoming Actin, Consensus refinement |
Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-MG: ![]() ChemComp-ATP: |
Source |
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![]() | CYTOSOLIC PROTEIN / Actin / Filament / Elongation / Ends / Formin / Severing |