6SXA

XPF-ERCC1 Cryo-EM Structure, Apo-form

Summary for 6SXA

• Entry DOI: 10.2210/pdb6sxa/pdb
• EMDB information: 10337
• Descriptor: DNA repair endonuclease XPF, DNA excision repair protein ERCC-1 (2 entities in total)
• Functional Keywords: dna repair enzyme. nucleotide excision repair, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 137234.46

Authors

Jones, M.L.,Briggs, D.C.,McDonald, N.Q. (deposition date: 2019-09-25, release date: 2020-03-11, Last modification date: 2024-05-22)

Primary citation

Jones, M.,Beuron, F.,Borg, A.,Nans, A.,Earl, C.P.,Briggs, D.C.,Snijders, A.P.,Bowles, M.,Morris, E.P.,Linch, M.,McDonald, N.Q.
Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.
Nat Commun, 11:1120-1120, 2020

PubMed Abstract: The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated by DNA junction substrates is not currently understood. Here we report cryo-electron microscopy structures of both DNA-free and DNA-bound human XPF-ERCC1. DNA-free XPF-ERCC1 adopts an auto-inhibited conformation in which the XPF helical domain masks the ERCC1 (HhH) domain and restricts access to the XPF catalytic site. DNA junction engagement releases the ERCC1 (HhH) domain to couple with the XPF-ERCC1 nuclease/nuclease-like domains. Structure-function data indicate xeroderma pigmentosum patient mutations frequently compromise the structural integrity of XPF-ERCC1. Fanconi anaemia patient mutations in XPF often display substantial in-vitro activity but are resistant to activation by ICLR recruitment factor SLX4. Our data provide insights into XPF-ERCC1 architecture and catalytic activation.

PubMed: 32111838
DOI: 10.1038/s41467-020-14856-2

Experimental method

ELECTRON MICROSCOPY (3.6 Å)