INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Nature communications - 12(2021), 1 vom: 12. Mai, Seite 2743 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dixit, Updesh [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 28.05.2021 Date Revised 01.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-021-22733-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325322627 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325322627 | ||
| 003 | DE-627 | ||
| 005 | 20240201231823.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-021-22733-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1277.xml |
| 035 | |a (DE-627)NLM325322627 | ||
| 035 | |a (NLM)33980829 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dixit, Updesh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.05.2021 | ||
| 500 | |a Date Revised 01.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a SMARCB1 Protein |2 NLM | |
| 650 | 7 | |a SMARCB1 protein, human |2 NLM | |
| 650 | 7 | |a HIV Integrase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.- |2 NLM | |
| 650 | 7 | |a p31 integrase protein, Human immunodeficiency virus 1 |2 NLM | |
| 650 | 7 | |a YY6481J2FF |2 NLM | |
| 700 | 1 | |a Bhutoria, Savita |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Liming |e verfasserin |4 aut | |
| 700 | 1 | |a Spira, Menachem |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Sheeba |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Adams, Lucas J |e verfasserin |4 aut | |
| 700 | 1 | |a Cahill, Sean |e verfasserin |4 aut | |
| 700 | 1 | |a Pathak, Rajiv |e verfasserin |4 aut | |
| 700 | 1 | |a Rajesh Kumar, P |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Minh |e verfasserin |4 aut | |
| 700 | 1 | |a Acharya, Seetharama A |e verfasserin |4 aut | |
| 700 | 1 | |a Brenowitz, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Almo, Steven C |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Xiaoqin |e verfasserin |4 aut | |
| 700 | 1 | |a Steven, Alasdair C |e verfasserin |4 aut | |
| 700 | 1 | |a Cowburn, David |e verfasserin |4 aut | |
| 700 | 1 | |a Girvin, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Kalpana, Ganjam V |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 12(2021), 1 vom: 12. Mai, Seite 2743 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2021 |g number:1 |g day:12 |g month:05 |g pages:2743 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-021-22733-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2021 |e 1 |b 12 |c 05 |h 2743 | ||