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Structure. 2019 Aug 6;27(8):1234-1245.e5. doi: 10.1016/j.str.2019.04.015. Epub 2019 May 30.

MxB Restricts HIV-1 by Targeting the Tri-hexamer Interface of the Viral Capsid.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
2
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA.
3
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. Electronic address: yong.xiong@yale.edu.

Abstract

The human antiviral protein MxB is a restriction factor that fights HIV infection. Previous experiments have demonstrated that MxB targets the HIV capsid, a protein shell that protects the viral genome. To make the conical-shaped capsid, HIV CA proteins are organized into a lattice composed of hexamer and pentamer building blocks, providing many interfaces for host proteins to recognize. Through extensive biochemical and biophysical studies and molecular dynamics simulations, we show that MxB is targeting the HIV capsid by recognizing the region created at the intersection of three CA hexamers. We are further able to map this interaction to a few CA residues, located in a negatively charged well at the interface between the three CA hexamers. This work provides detailed residue-level mapping of the targeted capsid interface and how MxB interacts. This information could inspire the development of capsid-targeting therapies for HIV.

KEYWORDS:

HIV; MxB; capsid; molecular dynamics; pattern-sensing; simulation

PMID:
31155311
DOI:
10.1016/j.str.2019.04.015

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