Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex.
Journal, issue, pages	Nucleic Acids Res, Vol. 49, Issue 1, Page 306-321, Year 2021
Publish date	Jan 11, 2021
Authors	Michal Hammel / Ishtiaque Rashid / Aleksandr Sverzhinsky / Yasin Pourfarjam / Miaw-Sheue Tsai / Tom Ellenberger / John M Pascal / In-Kwon Kim / John A Tainer / Alan E Tomkinson /
PubMed Abstract	The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined ...The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined biophysical approaches to gain insights into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. Structurally-guided mutational analyses based on the crystal structure of the human BRCT-BRCT heterodimer identified the network of salt bridges that together with the N-terminal extension of the XRCC1 C-terminal BRCT domain constitute the XL molecular interface. Coupling size exclusion chromatography with small angle X-ray scattering and multiangle light scattering (SEC-SAXS-MALS), we determined that the XL is more compact than either XRCC1 or LigIIIα, both of which form transient homodimers and are highly disordered. The reduced disorder and flexibility allowed us to build models of XL particles visualized by negative stain electron microscopy that predict close spatial organization between the LigIIIα catalytic core and both BRCT domains of XRCC1. Together our results identify an atypical BRCT-BRCT interaction as the stable nucleating core of the XL that links the flexible nick sensing and catalytic domains of LigIIIα to other protein partners of the flexible XRCC1 scaffold.
External links	Nucleic Acids Res / PubMed:33330937 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.4 - 31.5 Å
Structure data	EMDB-22130: The negative stain EM structure of the human DNA LigIIIalpha-XRCC1 complex; conformer 1 Method: EM (single particle) / Resolution: 31.0 Å EMDB-22307: The negative stain EM structure of the human DNA LigIIIalpha-XRCC1 complex; conformer 2 Method: EM (single particle) / Resolution: 31.5 Å PDB-6wh1: Structure of the complex of human DNA ligase III-alpha and XRCC1 BRCT domains Method: X-RAY DIFFRACTION / Resolution: 2.4 Å PDB-6wh2: Structure of the C-terminal BRCT domain of human XRCC1 Method: X-RAY DIFFRACTION / Resolution: 2.414 Å
Chemicals	ChemComp-HOH: WATER
Source	homo sapiens (human)
Keywords	DNA BINDING PROTEIN/LIGASE / DNA ligase complex / DNA repair / DNA BINDING PROTEIN / DNA BINDING PROTEIN-LIGASE complex