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8UNH

Cryo-EM structure of T4 Bacteriophage Clamp Loader with Sliding Clamp

8UNH の概要
エントリーDOI10.2210/pdb8unh/pdb
関連するPDBエントリー8UNF
EMDBエントリー42399 42402
分子名称Sliding-clamp-loader large subunit, Sliding-clamp-loader small subunit, Sliding clamp, ... (5 entities in total)
機能のキーワードautoinhibited, dna-free, catalytically inactive, stable, replication
由来する生物種Tequatrovirus T4
詳細
タンパク質・核酸の鎖数8
化学式量合計240467.49
構造登録者
Huang, Y.,Marcus, K.,Subramanian, S.,Gee, L.C.,Gorday, K.,Ghaffari-Kashani, S.,Luo, X.,Zhang, L.,O'Donnell, M.,Subramanian, S.,Kuriyan, J. (登録日: 2023-10-19, 公開日: 2023-12-13, 最終更新日: 2024-04-03)
主引用文献Marcus, K.,Huang, Y.,Subramanian, S.,Gee, C.L.,Gorday, K.,Ghaffari-Kashani, S.,Luo, X.R.,Zheng, L.,O'Donnell, M.,Subramaniam, S.,Kuriyan, J.
Autoinhibition of a clamp-loader ATPase revealed by deep mutagenesis and cryo-EM.
Nat.Struct.Mol.Biol., 31:424-435, 2024
Cited by
PubMed Abstract: Clamp loaders are AAA+ ATPases that facilitate high-speed DNA replication. In eukaryotic and bacteriophage clamp loaders, ATP hydrolysis requires interactions between aspartate residues in one protomer, present in conserved 'DEAD-box' motifs, and arginine residues in adjacent protomers. We show that functional defects resulting from a DEAD-box mutation in the T4 bacteriophage clamp loader can be compensated by widely distributed single mutations in the ATPase domain. Using cryo-EM, we discovered an unsuspected inactive conformation of the clamp loader, in which DNA binding is blocked and the catalytic sites are disassembled. Mutations that restore function map to regions of conformational change upon activation, suggesting that these mutations may increase DNA affinity by altering the energetic balance between inactive and active states. Our results show that there are extensive opportunities for evolution to improve catalytic efficiency when an inactive intermediate is involved.
PubMed: 38177685
DOI: 10.1038/s41594-023-01177-3
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (3.21 Å)
構造検証レポート
Validation report summary of 8unh
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-12-18に公開中

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