6dbw

Cryo-EM structure of RAG in complex with 12-RSS substrate DNACryo-EM structure of RAG in complex with 12-RSS substrate DNA

6dbw, resolution 4.70Å Show:Asymmetric Unit Biological Assembly Structural highlights 6dbw is a 6 chain structure with sequence from Brachidanio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 6dbi, 6dbj, 6dbl, 6dbo, 6dbq, 6dbr, 6dbu, 6dbv, 6dbx Gene: rag1 (Brachidanio rerio), rag2 (Brachidanio rerio) Activity: RING-type E3 ubiquitin transferase, with EC number 2.3.2.27 Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. Publication Abstract from PubMed The mechanism for initiating DNA cleavage by DDE-family enzymes, including the RAG endonuclease, which initiates V(D)J recombination, is not well understood. Here we report six cryo-EM structures of zebrafish RAG in complex with one or two intact recombination signal sequences (RSSs), at up to 3.9-A resolution. Unexpectedly, these structures reveal DNA melting at the heptamer of the RSSs, thus resulting in a corkscrew-like rotation of coding-flank DNA and the positioning of the scissile phosphate in the active site. Substrate binding is associated with dimer opening and a piston-like movement in RAG1, first outward to accommodate unmelted DNA and then inward to wedge melted DNA. These precleavage complexes show limited base-specific contacts of RAG at the conserved terminal CAC/GTG sequence of the heptamer, thus suggesting conservation based on a propensity to unwind. CA and TG overwhelmingly dominate terminal sequences in transposons and retrotransposons, thereby implicating a universal mechanism for DNA melting during the initiation of retroviral integration and DNA transposition. DNA melting initiates the RAG catalytic pathway.,Ru H, Mi W, Zhang P, Alt FW, Schatz DG, Liao M, Wu H Nat Struct Mol Biol. 2018 Aug;25(8):732-742. doi: 10.1038/s41594-018-0098-5. Epub, 2018 Jul 30. PMID:30061602 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Recombination-activating gene 3D structures