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TitleINI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 2743, Year 2021
Publish dateMay 12, 2021
AuthorsUpdesh Dixit / Savita Bhutoria / Xuhong Wu / Liming Qiu / Menachem Spira / Sheeba Mathew / Richard Harris / Lucas J Adams / Sean Cahill / Rajiv Pathak / P Rajesh Kumar / Minh Nguyen / Seetharama A Acharya / Michael Brenowitz / Steven C Almo / Xiaoqin Zou / Alasdair C Steven / David Cowburn / Mark Girvin / Ganjam V Kalpana /
PubMed AbstractINI1/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 ...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 IC 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.
External linksNat Commun / PubMed:33980829 / PubMed Central
MethodsEM (tomography) / NMR (solution)
Structure data

EMDB-22410:
Cryo-electron tomography of HIV-1 integrase mutant, W235E
Method: EM (tomography)

EMDB-22411:
Cryo-electron tomography of HIV-1 integrase mutant, W235E
Method: EM (tomography)

PDB-6ax5:
RPT1 region of INI1/SNF5/SMARCB1_HUMAN - SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1.
Method: SOLUTION NMR

Source
  • homo sapiens (human)
KeywordsNUCLEAR PROTEIN / RPT1 / INI1 / actin-dependent regulator

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