Fig. 5: Comparison of DNA-free and DNA-bound XPF–ERCC1 gives insights into DNA-junction activation. | Nature Communications

Fig. 5: Comparison of DNA-free and DNA-bound XPF–ERCC1 gives insights into DNA-junction activation.

From: Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation

Fig. 5

a Two orthogonal views of DNA-free XPF–ERCC1 highlighting known ssDNA binding sites. An NMR structure of XPF (HhH)2 domain bound to a ssDNA (PDB: 2KN7) mapped on to the full-length DNA-free structure indicates a distance of ~50Å between the ssDNA-binding site and residues known to bind ssDNA in the ERCC1 NLD. b Equivalent views as in panel a for DNA-bound XPF–ERCC1 indicating the 2×(HhH)2 domain undergoes a substantial movement to engage the ERCC1 NLD. This positions the two ssDNA-binding sites close enough to simultaneously engage ssDNA. Inset shows only a stem loop is a substrate for XPF-ERCC1. c The XPF HLM from the DNA-bound structure contains a concave surface lines with basic residues (yellow) that could potentially bind to dsDNA. d Equivalent view to panel c of the helicase module from MDA5 bound to A-form dsRNA (PDB: 4GL2) through an equivalent positively charged concave surface. e Proposed model for XPF–ERCC1 domain rearrangements upon binding stem–loop DNA. Red arrows indicate direction of domain rearrangements from DNA-free to DNA-bound. Dotted yellow lines indicate domains that undergo significant conformational changes. Scissors indicate the approximate location of the active site.

Back to article page