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Structural analysis and molecular dynamics simulation studies of HIV-1 antisense protein predict its potential role in HIV replication and pathogenesis.

ABSTRACT: The functional significance of the HIV-1 Antisense Protein (ASP) has been a paradox since its discovery. The expression of this protein in HIV-1-infected cells and its involvement in autophagy, transcriptional regulation, and viral latency have sporadically been reported in various studies. Yet, the definite role of this protein in HIV-1 infection remains unclear. Deciphering the 3D structure of HIV-1 ASP would throw light on its potential role in HIV lifecycle and host-virus interaction. Hence, using extensive molecular modeling and dynamics simulation for 200 ns, we predicted the plausible 3D-structures of ASP from two reference strains of HIV-1 namely, Indie-C1 (subtype-C) and NL4-3 (subtype-B) so as to derive its functional implication through structural domain analysis. In spite of sequence and structural differences in subtype B and C ASP, both structures appear to share common domains like the Von Willebrand Factor Domain-A (VWFA), Integrin subunit alpha-X (ITGSX), and ETV6-Transcriptional repressor, thereby reiterating the potential role of HIV-1 ASP in transcriptional repression and autophagy, as reported in earlier studies. Gromos-based cluster analysis of the centroid structures also reassured the accuracy of the prediction. This is the first study to elucidate a highly plausible structure for HIV-1 ASP which could serve as a feeder for further experimental validation studies.

SUBMITTER: Sathiyamani B

PROVIDER: S-EPMC10067880 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Structural analysis and molecular dynamics simulation studies of HIV-1 antisense protein predict its potential role in HIV replication and pathogenesis.

Sathiyamani Balakumaran B Daniel Evangeline Ann EA Ansar Samdani S Esakialraj Bennett Henzeler BH Hassan Sameer S Revanasiddappa Prasanna D PD Keshavamurthy Amrutha A Roy Sujata S Vetrivel Umashankar U Hanna Luke Elizabeth LE

Frontiers in microbiology 20230320

The functional significance of the HIV-1 Antisense Protein (ASP) has been a paradox since its discovery. The expression of this protein in HIV-1-infected cells and its involvement in autophagy, transcriptional regulation, and viral latency have sporadically been reported in various studies. Yet, the definite role of this protein in HIV-1 infection remains unclear. Deciphering the 3D structure of HIV-1 ASP would throw light on its potential role in HIV lifecycle and host-virus interaction. Hence, ...[more]

PMID: 37020719

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Structural analysis and molecular dynamics simulation studies of HIV-1 antisense protein predict its potential role in HIV replication and pathogenesis.

Publications

Structural analysis and molecular dynamics simulation studies of HIV-1 antisense protein predict its potential role in HIV replication and pathogenesis.

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