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Journal article
Clade-Specific Alterations within the HIV-1 Capsid Protein with Implications for Nuclear Translocation
Biomolecules (Basel, Switzerland), v 12(5), p695
12 May 2022
PMID: 35625621
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The HIV-1 capsid (CA) protein has emerged as an attractive therapeutic target. However, all inhibitor designs and structural analyses for this essential HIV-1 protein have focused on the clade B HIV-1 (NL4-3) variant. This study creates, overproduces, purifies, and characterizes the CA proteins from clade A1, A2, B, C, and D isolates. These new CA constructs represent novel reagents that can be used in future CA-targeted inhibitor design and to investigate CA proteins' structural and biochemical properties from genetically diverse HIV-1 subtypes. Moreover, we used surface plasmon resonance (SPR) spectrometry and computational modeling to examine inter-clade differences in CA assembly and binding of PF-74, CPSF-6, and NUP-153. Interestingly, we found that HIV-1 CA from clade A1 does not bind to NUP-153, suggesting that the import of CA core structures through the nuclear pore complex may be altered for viruses from this clade. Overall, we have demonstrated that in silico generated models of the HIV-1 CA protein from clades other than the prototypically used clade B have utility in understanding and predicting biology and antiviral drug design and mechanism of action.
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Details
- Title
- Clade-Specific Alterations within the HIV-1 Capsid Protein with Implications for Nuclear Translocation
- Creators
- Alexej Dick - Drexel UniversityMegan E Meuser - Drexel UniversitySimon Cocklin - Drexel University
- Publication Details
- Biomolecules (Basel, Switzerland), v 12(5), p695
- Publisher
- MDPI
- Grant note
- AI150491 / NIH HHS NS089435 / NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000802400900001
- Scopus ID
- 2-s2.0-85129783830
- Other Identifier
- 991019168510804721
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- Web of Science research areas
- Biochemistry & Molecular Biology