2O8F

human MutSalpha (MSH2/MSH6) bound to DNA with a single base T insert

2O8F の概要

• エントリーDOI: 10.2210/pdb2o8f/pdb
• 関連するPDBエントリー: 2O8B 2O8C 2O8D 2O8E
• 分子名称: 5'-D(*GP*AP*CP*GP*GP*CP*CP*GP*CP*CP*GP*CP*TP*AP*GP*CP*G)-3', 5'-D(*CP*GP*CP*TP*AP*GP*CP*GP*TP*GP*CP*GP*GP*CP*CP*GP*TP*C)-3', DNA mismatch repair protein Msh2, ... (7 entities in total)
• 機能のキーワード: dna mismatch repair, dna damage response, somatic hypermutation, protein-dna complex, dna mispair, cancer, abc transporter atpase, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (Potential): P43246; Nucleus: P52701
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 232093.96

構造登録者

Warren, J.J.,Pohlhaus, T.J.,Changela, A.,Modrich, P.L.,Beese, L.S. (登録日: 2006-12-12, 公開日: 2007-06-05, 最終更新日: 2023-08-30)

主引用文献

Warren, J.J.,Pohlhaus, T.J.,Changela, A.,Iyer, R.R.,Modrich, P.L.,Beese, L.S.
Structure of the Human MutSalpha DNA Lesion Recognition Complex.
Mol.Cell, 26:579-592, 2007

PubMed Abstract: Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates the cellular response to certain classes of DNA damage, and has been implicated in the generation of immune diversity. Each of these functions depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein complex is responsible for tumor development in about half of known hereditary nonpolyposis colorectal cancer kindreds and also occurs in sporadic tumors in a variety of tissues. Here, we describe a series of crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR pathway. All lesions are recognized in a similar manner, indicating that diversity of MutSalpha-dependent responses to DNA lesions is generated in events downstream of this lesion recognition step. This study also allows rigorous mapping of cancer-causing mutations and furthermore suggests structural pathways for allosteric communication between different regions within the heterodimer.

PubMed: 17531815
DOI: 10.1016/j.molcel.2007.04.018

実験手法

X-RAY DIFFRACTION (3.25 Å)