ジャーナル: Nat Commun / 年: 2021 タイトル: INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication. 著者: Updesh 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 / ...著者: Updesh 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 / 要旨: 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 ...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.