Juntit, On-anong and Sornsuwan, Kanokporn and Wisitponchai, Tanchanok and Lee, Vannajan Sanghiran and Sakkhachornphop, Supachai and Yasamut, Umpa and Tayapiwatana, Chatchai (2023) Dimeric ankyrin with inverted module promotes bifunctional property in capturing capsid to impede HIV-1 replication. International Journal of Molecular Sciences, 24 (6). ISSN 1661-6596, DOI https://doi.org/10.3390/ijms24065266.
Full text not available from this repository.Abstract
Several anti-HIV scaffolds have been proposed as complementary treatments to highly active antiretroviral therapy. Ank(GAG)1D4, a designed ankyrin repeat protein, formerly demonstrated anti-HIV-1 replication by interfering with HIV-1 Gag polymerization. However, the improvement of the effectiveness was considered. Recently, the dimeric molecules of Ank(GAG)1D4 were accomplished in enhancing the binding activity against HIV-1 capsid (CAp24). In this study, the interaction of CAp24 against the dimer conformations was elucidated to elaborate the bifunctional property. The accessibility of the ankyrin binding domains was inspected by bio-layer interferometry. By inverting the second module of dimeric ankyrin (Ank(GAG)1D4(NC-CN)), the CAp24 interaction K-D was significantly reduced. This reflects the capability of Ank(GAG)1D4(NC-CN) in simultaneously capturing CAp24. On the contrary, the binding activity of dimeric Ank(GAG)1D4(NC-NC) was indistinguishable from the monomeric Ank(GAG)1D4. The bifunctional property of Ank(GAG)1D4(NC-CN) was subsequently confirmed in the secondary reaction with additional p17p24. This data correlates with the MD simulation, which suggested the flexibility of the Ank(GAG)1D4(NC-CN) structure. The CAp24 capturing capacity was influenced by the distance of the Ank(GAG)1D4 binding domains to introduce the avidity mode of Ank(GAG)1D4(NC-CN). Consequently, Ank(GAG)1D4(NC-CN) showed superior potency in interfering with HIV-1 NL4-3 WT and HIV-1 NL4-3 MIRCAI201V replication than Ank(GAG)1D4(NC-NC) and an affinity improved Ank(GAG)1D4-S45Y.
| Item Type: | Article |
|---|---|
| Funders: | Distinguished Research Professor of the National Research Council of Thailand NRCT 808/2563 |
| Uncontrolled Keywords: | HIV-1 assembly; dimeric DARPin; inverted ankyrin; replication inhibitor; HIV-1 drug-resistant |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Science > Department of Chemistry |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 24 Nov 2023 08:23 |
| Last Modified: | 24 Nov 2023 08:23 |
| URI: | http://eprints.um.edu.my/id/eprint/38511 |
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