EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	NPF binding to Arp2 is allosterically linked to the release of ArpC5's N-terminal tail and conformational changes in Arp2/3 complex.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 8, Page e2421557122, Year 2025
掲載日	2025年2月25日
著者	Andrew J Saks / Kyle R Barrie / Grzegorz Rebowski / Roberto Dominguez /
PubMed 要旨	Arp2/3 complex generates branched actin networks essential for numerous motile functions of the cell. It comprises seven subunits: actin-related proteins (Arps) 2 and 3 and five scaffolding subunits ...Arp2/3 complex generates branched actin networks essential for numerous motile functions of the cell. It comprises seven subunits: actin-related proteins (Arps) 2 and 3 and five scaffolding subunits (ArpC1-5). The complex adopts two major conformations: inactive, with the Arps interacting end-to-end, and active, with the Arps aligned side-by-side like subunits in the actin filament. Activation involves several cofactors, including ATP, WASP-family nucleation-promoting factors (NPFs), actin monomers, and the mother actin filament. NPFs bind to two sites, one on Arp2-ArpC1 and one on Arp3, delivering actin subunits at the barbed end of the Arps to initiate branch elongation. However, the mechanisms by which each NPF drives the equilibrium toward activation remain unclear. We present two cryo-electron microscopy (cryo-EM) structures of Arp2/3 complex at 2.9-Å resolution: one with NPFs bound to Arp3 and ArpC1 but not Arp2 and another with NPFs bound to Arp3 and Arp2-ArpC1. The structures reveal that NPF binding to Arp2 is allosterically linked to the release of ArpC5's N-terminal tail from Arp2 and conformational changes in Arp2, including closure of its ATP-binding cleft and partial rotation and translation toward its position in the active complex at the branch. Previous work identified another allosteric switch linking NPF binding to Arp3 with the release of its inhibitory C-terminal tail, which we also observe. In summary, both NPF-binding sites induce allosteric changes in Arp2/3 complex, collectively shifting the equilibrium toward activation.
リンク	Proc Natl Acad Sci U S A / PubMed:40042350 / PubMed Central
手法	EM (単粒子)
解像度	2.85 - 3.41 Å
構造データ	EMDB-46913: local refinement of Arp3 and ArpC2 手法: EM (単粒子) / 解像度: 2.85 Å EMDB-46924: local refinement of ArpC3 for Arp 2/3 complex bound to NPFs 手法: EM (単粒子) / 解像度: 3.03 Å EMDB-46925: local refinement of arpC5, arpC1 and arp2 for arp 2/3 complex with 1 of 2 NPFs dissociated and arpC5 tail bound 手法: EM (単粒子) / 解像度: 3.41 Å EMDB-46926: Local refinement of ArpC4 for Arp 2/3 complex bound to NPFs 手法: EM (単粒子) / 解像度: 2.88 Å EMDB-46934: local refinement of arpC5, arpC1 and arp2 for arp 2/3 complex 2 NPFs bound and arpC5 tail mostly dissociated 手法: EM (単粒子) / 解像度: 2.91 Å 46992 9dlx EMDB-46992, PDB-9dlx: Bovine Arp2/3 complex with N-WASP CA bound to Arp3 and Arp2-ArpC1 手法: EM (単粒子) / 解像度: 2.91 Å 46993 9dlz EMDB-46993, PDB-9dlz: Bovine Arp2/3 complex with N-WASP CA bound to Arp3 手法: EM (単粒子) / 解像度: 3.4 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, エネルギー貯蔵分子YM ChemComp-MG*: Unknown entry
由来	bos taurus (ウシ) homo sapiens (ヒト)
キーワード	STRUCTURAL PROTEIN / actin / arp 2-3 complex / N-WASP / nucleation promoting factor