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-Structure paper
| タイトル | PCNA is a nucleotide exchange factor for the clamp loader ATPase complex. |
|---|---|
| ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 122, Issue 46, Page e2518834122, Year 2025 |
| 掲載日 | 2025年11月18日 |
著者 | Joshua Pajak / Jacob T Landeck / Xingchen Liu / Krishna Anand / Sasha Litvak / Brian A Kelch / ![]() |
| PubMed 要旨 | All life requires loading ring-shaped sliding clamp protein complexes onto DNA. The sliding clamp loader is a conserved AAA+ ATPase that binds the sliding clamp, opens the ring, and places it onto ...All life requires loading ring-shaped sliding clamp protein complexes onto DNA. The sliding clamp loader is a conserved AAA+ ATPase that binds the sliding clamp, opens the ring, and places it onto DNA. While recent structural work on both the canonical and "alternative" clamp loaders has shed light into how these machines perform their task once, it remains unclear how clamp loaders are recycled to load multiple sliding clamps. Here, we present structures of the clamp loader Replication Factor C (RFC) in absence of sliding clamp or supplemented nucleotide. Our structures indicate that RFC holds onto ADP tightly in at least two of its four ATPase active sites, suggesting that nucleotide exchange is regulated. Our molecular dynamics simulations and biochemical data indicate that binding of the sliding clamp Proliferating Cell Nuclear Antigen (PCNA) causes rapid exchange of tightly bound ADP. Our data suggest that PCNA acts as a nucleotide exchange factor (NEF) by prying apart adjacent subunits, providing a pathway for ADP release. We propose that, by using its own substrate as a NEF, RFC excludes off-pathway states that would arise from binding DNA prior to PCNA. |
リンク | Proc Natl Acad Sci U S A / PubMed:41231947 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.57 - 2.63 Å |
| 構造データ | EMDB-71572, PDB-9peo: EMDB-71574, PDB-9per: EMDB-71575, PDB-9pes: EMDB-71576, PDB-9pet: EMDB-71577, PDB-9peu: EMDB-71578, PDB-9pev: |
| 化合物 | ![]() ChemComp-ACT: ![]() ChemComp-ADP: ![]() ChemComp-GDP: |
| 由来 |
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キーワード | REPLICATION / AAA+ ATPase / Rossmann Fold / Complex / DNA replication |
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