6NUA

DNA-protein crosslink between E. coli YedK and ssDNA containing an abasic site

6NUA の概要

• エントリーDOI: 10.2210/pdb6nua/pdb
• 分子名称: SOS response-associated peptidase YedK, DNA (5'-D(*GP*TP*CP*(PED)P*GP*GP*A)-3') (3 entities in total)
• 機能のキーワード: dna-protein crosslink, abasic site, thiazolidine, replication stress, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55276.49

構造登録者

Eichman, B.F.,Amidon, K.M. (登録日: 2019-01-31, 公開日: 2019-06-26, 最終更新日: 2024-10-09)

主引用文献

Thompson, P.S.,Amidon, K.M.,Mohni, K.N.,Cortez, D.,Eichman, B.F.
Protection of abasic sites during DNA replication by a stable thiazolidine protein-DNA cross-link.
Nat.Struct.Mol.Biol., 26:613-618, 2019

PubMed Abstract: Abasic (AP) sites are one of the most common DNA lesions that block replicative polymerases. 5-hydroxymethylcytosine binding, embryonic stem cell-specific protein (HMCES) recognizes and processes these lesions in the context of single-stranded DNA (ssDNA). A HMCES DNA-protein cross-link (DPC) intermediate is thought to shield the AP site from endonucleases and error-prone polymerases. The highly evolutionarily conserved SOS-response associated peptidase (SRAP) domain of HMCES and its Escherichia coli ortholog YedK mediate lesion recognition. Here we uncover the basis of AP site protection by SRAP domains from a crystal structure of the YedK DPC. YedK forms a stable thiazolidine linkage between a ring-opened AP site and the α-amino and sulfhydryl substituents of its amino-terminal cysteine residue. The thiazolidine linkage explains the remarkable stability of the HMCES DPC, its resistance to strand cleavage and the proteolysis requirement for resolution. Furthermore, its structure reveals that HMCES has specificity for AP sites in ssDNA at junctions found when replicative polymerases encounter the AP lesion.

PubMed: 31235915
DOI: 10.1038/s41594-019-0255-5

実験手法

X-RAY DIFFRACTION (1.64 Å)