7u32

MVV cleaved synaptic complex (CSC) intasome at 3.4 A resolution

spinqualitylabelsall models 7u32, resolution 3.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7u32 is a 20 chain structure with sequence from Visna/maedi virus EV1 KV1772 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.46Å Ligands: CA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function POL_VILVK During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the host chromosome by the viral integrase enzyme. RNase H activity is associated with the reverse transcriptase. Publication Abstract from PubMed A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into a host cell genome. Reconstitution of the intasome from the maedi-visna virus (MVV), an ovine lentivirus, revealed a large assembly containing sixteen IN subunits(1). Herein, we report cryo-EM structures of the lentiviral intasome prior to engagement of target DNA and following strand transfer, refined at 3.4 and 3.5 A resolution, respectively. The structures elucidate details of the protein-protein and protein-DNA interfaces involved in lentiviral intasome formation. We show that the homomeric interfaces involved in IN hexadecamer formation and the alpha-helical configuration of the linker connecting the C-terminal and catalytic core domains are critical for MVV IN strand transfer activity in vitro and for virus infectivity. Single-molecule microscopy in conjunction with photobleaching reveals that the MVV intasome can bind a variable number, up to sixteen molecules, of the lentivirus-specific host factor LEDGF/p75. Concordantly, ablation of endogenous LEDGF/p75 results in gross redistribution of MVV integration sites in human and ovine cells. Our data confirm the importance of the expanded architecture observed in cryo-EM studies of lentiviral intasomes and suggest that this organization underlies multivalent interactions with chromatin for integration targeting to active genes. Multivalent interactions essential for lentiviral integrase function.,Ballandras-Colas A, Chivukula V, Gruszka DT, Shan Z, Singh PK, Pye VE, McLean RK, Bedwell GJ, Li W, Nans A, Cook NJ, Fadel HJ, Poeschla EM, Griffiths DJ, Vargas J, Taylor IA, Lyumkis D, Yardimci H, Engelman AN, Cherepanov P Nat Commun. 2022 May 3;13(1):2416. doi: 10.1038/s41467-022-29928-8. PMID:35504909 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Retroviral integrase 3D structures

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