6OE7

Crystal structure of HMCES cross-linked to DNA abasic site

Summary for 6OE7

• Entry DOI: 10.2210/pdb6oe7/pdb
• Descriptor: 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)
• Functional Keywords: 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
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 37367.48

Authors

Halabelian, L.,Li, Y.,Zeng, H.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Structural Genomics Consortium (SGC) (deposition date: 2019-03-27, release date: 2019-04-24, Last modification date: 2019-07-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)