5AKD

MutS in complex with the N-terminal domain of MutL - crystal form 3

5AKD の概要

• エントリーDOI: 10.2210/pdb5akd/pdb
• 関連するPDBエントリー: 5AKB 5AKC
• 分子名称: DNA MISMATCH REPAIR PROTEIN MUTS, DNA MISMATCH REPAIR PROTEIN MUTL, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: dna binding protein, dna mismatch repair, complex, sliding clamp, crosslinking
• 由来する生物種: ESCHERICHIA COLI; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 787548.12

構造登録者

Groothuizen, F.S.,Winkler, I.,Cristovao, M.,Fish, A.,Winterwerp, H.H.K.,Reumer, A.,Marx, A.D.,Hermans, N.,Nicholls, R.A.,Murshudov, G.N.,Lebbink, J.H.G.,Friedhoff, P.,Sixma, T.K. (登録日: 2015-03-03, 公開日: 2015-07-22, 最終更新日: 2024-01-10)

主引用文献

Groothuizen, F.S.,Winkler, I.,Cristovao, M.,Fish, A.,Winterwerp, H.H.,Reumer, A.,Marx, A.D.,Hermans, N.,Nicholls, R.A.,Murshudov, G.N.,Lebbink, J.H.,Friedhoff, P.,Sixma, T.K.
MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.
Elife, 4:e06744-e06744, 2015

PubMed Abstract: To avoid mutations in the genome, DNA replication is generally followed by DNA mismatch repair (MMR). MMR starts when a MutS homolog recognizes a mismatch and undergoes an ATP-dependent transformation to an elusive sliding clamp state. How this transient state promotes MutL homolog recruitment and activation of repair is unclear. Here we present a crystal structure of the MutS/MutL complex using a site-specifically crosslinked complex and examine how large conformational changes lead to activation of MutL. The structure captures MutS in the sliding clamp conformation, where tilting of the MutS subunits across each other pushes DNA into a new channel, and reorientation of the connector domain creates an interface for MutL with both MutS subunits. Our work explains how the sliding clamp promotes loading of MutL onto DNA, to activate downstream effectors. We thus elucidate a crucial mechanism that ensures that MMR is initiated only after detection of a DNA mismatch.

PubMed: 26163658
DOI: 10.7554/eLife.06744

実験手法

X-RAY DIFFRACTION (7.6 Å)