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Dimeric Ankyrin with Inverted Module Promotes Bifunctional Property in Capturing Capsid to Impede HIV-1 Replication

International Journal of Molecular Sciences, ISSN: 1422-0067, Vol: 24, Issue: 6
2023
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Most Recent News

Report Summarizes HIV/AIDS Study Findings from Chiang Mai University (Dimeric Ankyrin with Inverted Module Promotes Bifunctional Property in Capturing Capsid to Impede HIV-1 Replication)

2023 APR 12 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Daily -- Researchers detail new data in HIV/AIDS. According to news reporting

Article Description

Several anti-HIV scaffolds have been proposed as complementary treatments to highly active antiretroviral therapy. Ank1D4, 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 Ank1D4 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 (Ank1D4), the CAp24 interaction K was significantly reduced. This reflects the capability of Ank1D4 in simultaneously capturing CAp24. On the contrary, the binding activity of dimeric Ank1D4 was indistinguishable from the monomeric Ank1D4. The bifunctional property of Ank1D4 was subsequently confirmed in the secondary reaction with additional p17p24. This data correlates with the MD simulation, which suggested the flexibility of the Ank1D4 structure. The CAp24 capturing capacity was influenced by the distance of the Ank1D4 binding domains to introduce the avidity mode of Ank1D4. Consequently, Ank1D4 showed superior potency in interfering with HIV-1 NL4-3 WT and HIV-1 NL4-3 MIR replication than Ank1D4 and an affinity improved Ank1D4-S45Y.

Bibliographic Details

Juntit, On-Anong; Sornsuwan, Kanokporn; Wisitponchai, Tanchanok; Sanghiran Lee, Vannajan; Sakkhachornphop, Supachai; Yasamut, Umpa; Tayapiwatana, Chatchai

MDPI AG

Chemical Engineering; Biochemistry, Genetics and Molecular Biology; Chemistry; Computer Science

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