6OE7

Crystal structure of HMCES cross-linked to DNA abasic site

6OE7 の概要

• エントリーDOI: 10.2210/pdb6oe7/pdb
• 分子名称: Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein, DNA (5'-D(*GP*TP*CP*TP*GP*G)-3'), DNA (5'-D(*CP*CP*AP*GP*AP*CP*GP*TP*(DRZ)P*GP*TP*T)-3'), ... (6 entities in total)
• 機能のキーワード: srap domain, dna-binding, structural genomics, structural genomics consortium, sgc, hmces, protein-dna complex, dna damage protein, 3' overhang, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 37367.48

構造登録者

Halabelian, L.,Li, Y.,Zeng, H.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Structural Genomics Consortium (SGC) (登録日: 2019-03-27, 公開日: 2019-04-24, 最終更新日: 2019-07-17)

主引用文献

Halabelian, L.,Ravichandran, M.,Li, Y.,Zeng, H.,Rao, A.,Aravind, L.,Arrowsmith, C.H.
Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition.
Nat.Struct.Mol.Biol., 26:607-612, 2019

PubMed Abstract: Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein (HMCES) can covalently cross-link to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, we report crystal structures of the human HMCES SOS response-associated peptidase (SRAP) domain in complex with DNA-damage substrates, including HMCES cross-linked with an abasic site within a 3' overhang DNA. HMCES interacts with both single-strand and duplex segments of DNA, with two independent duplex DNA interaction sites identified in the SRAP domain. The HMCES DNA-protein cross-link structure provides structural insights into a novel thiazolidine covalent interaction between the DNA abasic site and conserved Cys 2 of HMCES. Collectively, our structures demonstrate the capacity for the SRAP domain to interact with a variety of single-strand- and double-strand-containing DNA structures found in DNA-damage sites, including 5' and 3' overhang DNAs and gapped DNAs with short single-strand segments.

PubMed: 31235913
DOI: 10.1038/s41594-019-0246-6

実験手法

X-RAY DIFFRACTION (2.2 Å)