SNAP output for PDB entry 6sxb [SNAP web server]

PDB-id

6sxb; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

cryo-EM (7.9 Å)

Summary

Xpf-ercc1 cryo-EM structure, DNA-bound form

Reference

Jones M, Beuron F, Borg A, Nans A, Earl CP, Briggs DC, Snijders AP, Bowles M, Morris EP, Linch M, McDonald NQ (2020): "Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation." Nat Commun, 11, 1120. doi: 10.1038/s41467-020-14856-2.

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)₂ domain and restricts access to the XPF catalytic site. DNA junction engagement releases the ERCC1 (HhH)₂ 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.