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6AX5

RPT1 region of INI1/SNF5/SMARCB1_HUMAN - SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1.

Summary for 6AX5
Entry DOI10.2210/pdb6ax5/pdb
NMR InformationBMRB: 27243
DescriptorSWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (1 entity in total)
Functional Keywordsrpt1, ini1, actin-dependent regulator, nuclear protein
Biological sourceHomo sapiens (Human)
Cellular locationNucleus: Q12824
Total number of polymer chains1
Total formula weight9572.92
Authors
Girvin, M.E.,Cahill, S.M.,Harris, R.,Cowburn, D.,Spira, M.,Wu, X.,Prakash, R.,Bernowitz, M.,Almo, S.C.,Kalpana, G.V. (deposition date: 2017-09-06, release date: 2017-10-18, Last modification date: 2024-05-15)
Primary citationDixit, U.,Bhutoria, S.,Wu, X.,Qiu, L.,Spira, M.,Mathew, S.,Harris, R.,Adams, L.J.,Cahill, S.,Pathak, R.,Rajesh Kumar, P.,Nguyen, M.,Acharya, S.A.,Brenowitz, M.,Almo, S.C.,Zou, X.,Steven, A.C.,Cowburn, D.,Girvin, M.,Kalpana, G.V.
INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication.
Nat Commun, 12:2743-2743, 2021
Cited by
PubMed 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 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.
PubMed: 33980829
DOI: 10.1038/s41467-021-22733-9
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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