4L6P

Structure of C22Y Mutant PCNA protein defective in DNA mismatch repair

4L6P の概要

• エントリーDOI: 10.2210/pdb4l6p/pdb
• 関連するPDBエントリー: 4L60
• 分子名称: Proliferating cell nuclear antigen, GLYCEROL (3 entities in total)
• 機能のキーワード: dna mismatch repair, dna replication, translesion synthesis, ubiquitylation, sumoylation, nucleus, dna binding protein
• 由来する生物種: Saccharomyces cerevisiae S288c (Baker's yeast)
• 細胞内の位置: Nucleus: P15873
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 89683.06

構造登録者

Washington, T.,Boehm, E. (登録日: 2013-06-12, 公開日: 2014-10-01, 最終更新日: 2023-09-20)

主引用文献

Dieckman, L.M.,Boehm, E.M.,Hingorani, M.M.,Washington, M.T.
Distinct structural alterations in proliferating cell nuclear antigen block DNA mismatch repair.
Biochemistry, 52:5611-5619, 2013

PubMed Abstract: During DNA replication, mismatches and small loops in the DNA resulting from insertions or deletions are repaired by the mismatch repair (MMR) machinery. Proliferating cell nuclear antigen (PCNA) plays an important role in both mismatch-recognition and resynthesis stages of MMR. Previously, two mutant forms of PCNA were identified that cause defects in MMR with little, if any, other defects. The C22Y mutant PCNA protein completely blocks MutSα-dependent MMR, and the C81R mutant PCNA protein partially blocks both MutSα-dependent and MutSβ-dependent MMR. In order to understand the structural and mechanistic basis by which these two amino acid substitutions in PCNA proteins block MMR, we solved the X-ray crystal structures of both mutant proteins and carried out further biochemical studies. We found that these amino acid substitutions lead to subtle, distinct structural changes in PCNA. The C22Y substitution alters the positions of the α-helices lining the central hole of the PCNA ring, whereas the C81R substitution creates a distortion in an extended loop near the PCNA subunit interface. We conclude that the structural integrity of the α-helices lining the central hole and this loop are both necessary to form productive complexes with MutSα and mismatch-containing DNA.

PubMed: 23869605
DOI: 10.1021/bi400378e

実験手法

X-RAY DIFFRACTION (2.68 Å)