4KHW

Ternary complex of RB69 mutant L415F with ribonucleotide at -2 position

4KHW の概要

• エントリーDOI: 10.2210/pdb4khw/pdb
• 関連するPDBエントリー: 4KHQ 4KHS 4KHU 4KHY 4KI4 4KI6
• 分子名称: DNA polymerase, DNA/RNA (5'-D(*AP*CP*AP*G)-R(P*G)-D(P*TP*AP*AP*GP*CP*AP*GP*TP*CP*CP*GP*CP*G)-3'), DNA (5'-D(*GP*CP*GP*GP*AP*CP*TP*GP*CP*TP*TP*AP*CP*C)-3'), ... (7 entities in total)
• 機能のキーワード: ribonucleotide, transferase-dna complex, transferase/dna
• 由来する生物種: Enterobacteria phage RB69
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 115361.30

構造登録者

Clausen, A.R.,Pedersen, L.C. (登録日: 2013-05-01, 公開日: 2013-10-09, 最終更新日: 2024-02-28)

主引用文献

Clausen, A.R.,Murray, M.S.,Passer, A.R.,Pedersen, L.C.,Kunkel, T.A.
Structure-function analysis of ribonucleotide bypass by B family DNA replicases.
Proc.Natl.Acad.Sci.USA, 110:16802-16807, 2013

PubMed Abstract: Ribonucleotides are frequently incorporated into DNA during replication, they are normally removed, and failure to remove them results in replication stress. This stress correlates with DNA polymerase (Pol) stalling during bypass of ribonucleotides in DNA templates. Here we demonstrate that stalling by yeast replicative Pols δ and ε increases as the number of consecutive template ribonucleotides increases from one to four. The homologous bacteriophage RB69 Pol also stalls during ribonucleotide bypass, with a pattern most similar to that of Pol ε. Crystal structures of an exonuclease-deficient variant of RB69 Pol corresponding to multiple steps in single ribonucleotide bypass reveal that increased stalling is associated with displacement of Tyr391 and an unpreferred C2'-endo conformation for the ribose. Even less efficient bypass of two consecutive ribonucleotides in DNA correlates with similar movements of Tyr391 and displacement of one of the ribonucleotides along with the primer-strand DNA backbone. These structure-function studies have implications for cellular signaling by ribonucleotides, and they may be relevant to replication stress in cells defective in ribonucleotide excision repair, including humans suffering from autoimmune disease associated with RNase H2 defects.

PubMed: 24082122
DOI: 10.1073/pnas.1309119110

実験手法

X-RAY DIFFRACTION (2.371 Å)