6sxb

XPF-ERCC1 Cryo-EM Structure, DNA-Bound form

spinqualitylabelsall models 6sxb, resolution 7.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6sxb is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 7.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease XPF_HUMAN Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:278760; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities. Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:610965. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly. Function XPF_HUMAN Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link. Publication Abstract from PubMed 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. Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.,Jones M, Beuron F, Borg A, Nans A, Earl CP, Briggs DC, Snijders AP, Bowles M, Morris EP, Linch M, McDonald NQ Nat Commun. 2020 Feb 28;11(1):1120. doi: 10.1038/s41467-020-14856-2. PMID:32111838 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Endonuclease 3D structures

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