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-Structure paper
| タイトル | Activation of Arp2/3 complex by a SPIN90 dimer in linear actin-filament nucleation. |
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| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 32, Issue 11, Page 2272-2284, Year 2025 |
| 掲載日 | 2025年9月15日 |
著者 | Justus Francis / Achyutha Krishna Pathri / Kankipati Teja Shyam / Sridhar Sripada / Rishav Mitra / Heidy Y Narvaez-Ortiz / Kiran Vyshnav Eliyan / Brad J Nolen / Saikat Chowdhury / ![]() |
| PubMed 要旨 | Arp2/3 complex is a key nucleator of actin filaments. It requires activation by nucleation-promoting factors (NPFs). WISH/DIP1/SPIN90 (WDS) proteins represent a unique class of NPFs that activate the ...Arp2/3 complex is a key nucleator of actin filaments. It requires activation by nucleation-promoting factors (NPFs). WISH/DIP1/SPIN90 (WDS) proteins represent a unique class of NPFs that activate the Arp2/3 complex independently of preexisting filaments, promoting linear actin-filament nucleation. In fission yeast, Dip1 binds to the clamp subunits in Arp2/3 complex to induce the short-pitch conformation, where Arp2 moves closer to Arp3 to mimic a filamentous actin dimer. However, how WDS proteins stimulate subunit flattening in Arp subunits, a 'scissor-like' conformational change akin to what is observed in an actin monomer during filament formation, remained unclear. Here we present cryo-electron microscopy structures of human SPIN90 bound to activated bovine Arp2/3 complex on an actin filament pointed end. The structures show that SPIN90 dimerizes through a metazoan-specific domain in the middle segment, engaging both the clamp and the Arp3/ARPC3 interface, to drive the activating conformational changes in Arp2/3 complex. Remarkably, a single SPIN90 dimer can also bridge two Arp2/3 complexes, enabling bidirectional actin nucleation and suggesting a mechanism for rapidly assembling complex actin network architectures. |
リンク | Nat Struct Mol Biol / PubMed:40954370 |
| 手法 | EM (単粒子) |
| 解像度 | 3.13 - 3.6 Å |
| 構造データ | EMDB-63642, PDB-9m5e: EMDB-63658, PDB-9m64: ![]() EMDB-63880: Focused Arp2/3 complex map of SPIN90 dimer-Arp2/3 complex-filament singlet complex structure ![]() EMDB-63883: Focused SPIN90-dimer map of SPIN90 dimer-Arp2/3 complex-filament singlet complex structure ![]() EMDB-63886: Focused actin filament map of SPIN90 dimer-Arp2/3 complex-filament singlet complex structure ![]() EMDB-63887: Arp2/3 complex from bottom half of SPIN90 dimer-Arp2/3 complex-actin filament Doublet complex ![]() EMDB-63888: Arp2/3 complex from the top half of SPIN90 dimer-Arp2/3 complex-actin filament Doublet complex ![]() EMDB-63889: Focused SPIN90-dimer of SPIN90 dimer-Arp2/3 complex-actin filament Doublet complex ![]() EMDB-63890: Focused filament from second half of SPIN90 dimer-Arp2/3 complex-actin filament Doublet complex ![]() EMDB-63891: Focused filament from one half of SPIN90 dimer-Arp2/3 complex-actin filament Doublet complex |
| 化合物 | ![]() ChemComp-MG: ![]() ChemComp-ADP: |
| 由来 |
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キーワード | CYTOSOLIC PROTEIN / SPIN90 / actin / cytoskeleton / Arp2-3 complex / Nucleation Promoting Factor |
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