HIV-1直接结合动力蛋白劫持微管运输机制

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-06-18 DOI:10.1126/sciadv.adn6796

Somayesadat Badieyan, Drew Lichon, Sevnur Komurlu Keceli, Michael P. Andreas, John P. Gillies, Wang Peng, Jiong Shi, Morgan E. DeSantis, Christopher R. Aiken, Till Böcking, Tobias W. Giessen, Edward M. Campbell, Michael A. Cianfrocco

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引用次数: 0

摘要

HIV-1在复制过程中利用微管细胞骨架到达宿主细胞核，然而对微管依赖性HIV-1运动的分子基础了解甚少。利用体外重构生物化学和单分子成像，我们发现HIV-1直接结合到逆行微管相关马达——动力蛋白上，而不是像之前所建议的那样，通过货物适配器。HIV-1衣壳晶格与动力蛋白尾部区域的辅助链结合。此外，我们还证明了附着在刚性载体（如HIV-1衣壳）上的多个动力蛋白马达，与膜质载体上的多个马达的行为不同，其运动性降低。我们的研究结果提供了一种最新的HIV-1运输模型，其中HIV-1直接与动力蛋白结合以“劫持”动力蛋白运输机制以实现微管运动。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

HIV-1 binds dynein directly to hijack microtubule transport machinery

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HIV-1 binds dynein directly to hijack microtubule transport machinery

HIV-1 uses the microtubule cytoskeleton to reach the host cell nucleus during replication, yet the molecular basis for microtubule-dependent HIV-1 motility is poorly understood. Using in vitro reconstitution biochemistry and single-molecule imaging, we found that HIV-1 binds to the retrograde microtubule-associated motor, dynein, directly and not via a cargo adaptor, as has been previously suggested. The HIV-1 capsid lattice binds to accessory chains on dynein’s tail domain. Further, we demonstrate that multiple dynein motors tethered to rigid cargoes, such as HIV-1 capsids, display reduced motility, distinct from the behavior of multiple motors on membranous cargoes. Our results provide an updated model of HIV-1 trafficking wherein HIV-1 binds to dynein directly to “hijack” the dynein transport machinery for microtubule motility.

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.