6PUT

Structure of HIV cleaved synaptic complex (CSC) intasome bound with calcium

Summary for 6PUT

• Entry DOI: 10.2210/pdb6put/pdb
• EMDB information: 20481
• Descriptor: Chimeric Sso7d and HIV-1 integrase, viral DNA transferred strand, viral DNA non-transferred strand, ... (6 entities in total)
• Functional Keywords: integrase, intasome, enzyme, transposition, viral protein, viral protein-dna complex, viral protein/dna
• Biological source: Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2); More
• Total number of polymer chains: 6
• Total formula weight: 185457.30

Authors

Lyumkis, D.,Jozwik, I.K.,Passos, D. (deposition date: 2019-07-18, release date: 2020-02-12, Last modification date: 2024-03-20)

Primary citation

Passos, D.O.,Li, M.,Jozwik, I.K.,Zhao, X.Z.,Santos-Martins, D.,Yang, R.,Smith, S.J.,Jeon, Y.,Forli, S.,Hughes, S.H.,Burke Jr., T.R.,Craigie, R.,Lyumkis, D.
Structural basis for strand-transfer inhibitor binding to HIV intasomes.
Science, 367:810-814, 2020

PubMed Abstract: The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have notable implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug-resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals.

PubMed: 32001521
DOI: 10.1126/science.aay8015

Experimental method

ELECTRON MICROSCOPY (2.9 Å)