EMD-22411

Tomography
EMD-22411 Deposition: 07/08/2020
Map released: 10/03/2021
Last modified: 26/05/2021
Overview Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-22411

Cryo-electron tomography of HIV-1 integrase mutant, W235E

EMD-22411

Tomography
EMD-22411 Deposition: 07/08/2020
Map released: 10/03/2021
Last modified: 26/05/2021
Overview Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1
Sample: Human immunodeficiency virus 1

Deposition Authors: Adams LJ, Steven AC
INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication.
PUBMED: 33980829
DOI: doi:10.1038/s41467-021-22733-9
ISSN: 2041-1723
Abstract:
INI1/SMARCB1 binds to HIV-1 integrase (IN) through its Rpt1 domain and exhibits multifaceted role in HIV-1 replication. Determining the NMR structure of INI1-Rpt1 and modeling its interaction with the IN-C-terminal domain (IN-CTD) reveal that INI1-Rpt1/IN-CTD interface residues overlap with those required for IN/RNA interaction. Mutational analyses validate our model and indicate that the same IN residues are involved in both INI1 and RNA binding. INI1-Rpt1 and TAR RNA compete with each other for IN binding with similar IC50 values. INI1-interaction-defective IN mutant viruses are impaired for incorporation of INI1 into virions and for particle morphogenesis. Computational modeling of IN-CTD/TAR complex indicates that the TAR interface phosphates overlap with negatively charged surface residues of INI1-Rpt1 in three-dimensional space, suggesting that INI1-Rpt1 domain structurally mimics TAR. This possible mimicry between INI1-Rpt1 and TAR explains the mechanism by which INI1/SMARCB1 influences HIV-1 late events and suggests additional strategies to inhibit HIV-1 replication.