MxB N-terminus adopts a stable α-helix to engage the HIV-1 capsid trimer interface
Abstract
The HIV-1 capsid, composed of capsid (CA) proteins arranged into a conical surface lattice, serves as a critical platform for host–pathogen interactions. Many host cofactors regulate HIV-1 infection by selectively recognizing the higher-order CA lattice rather than individual monomers or capsomers. Among these, Myxovirus resistance protein B (MxB) is a key cellular restriction factor that binds the capsid via its N-terminal fragment containing an arginine-rich motif (RRR), blocking HIV-1 infection at early infection stages. However, the structural basis of this interaction has remained elusive. Here, we present a structural characterization of the CA lattice in complex with the MxB N-terminal fragment using cryo-electron tomography and subtomogram averaging. Combining cryoEM structures with EM-guided all-atom molecular dynamics simulations, we identify residue-specific interactions between MxB and the CA trimer interfaces. Notably, residues 10-20 of the MxB N-terminus adopt an α-helical conformation that stabilizes binding at the CA trimer interface, revealing a distinct mode of capsid engagement. These findings provide insight into arginine-rich motif–mediated recognition by MxB and other host factors and establish a structural framework for the development of capsid-targeting antiviral therapeutics.
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BibTeX
@article{zhu2026nterminus,
title = {{MxB N-terminus adopts a stable α-helix to engage the HIV-1 capsid trimer interface}},
author = {Yanan Zhu and Juan S. Rey and Juan Shen and Juan R. Perilla and Peijun Zhang},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78493-x},
url = {https://www.nature.com/articles/s41467-026-78493-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MxB N-terminus adopts a stable α-helix to engage the HIV-1 capsid trimer interface
AU - Yanan Zhu
AU - Juan S. Rey
AU - Juan Shen
AU - Juan R. Perilla
AU - Peijun Zhang
PY - 2026
DA - 2026/10/16
JO - Nature Communications
DO - 10.1038/s41467-026-78493-x
UR - https://www.nature.com/articles/s41467-026-78493-x
AB - The HIV-1 capsid, composed of capsid (CA) proteins arranged into a conical surface lattice, serves as a critical platform for host–pathogen interactions. Many host cofactors regulate HIV-1 infection by selectively recognizing the higher-order CA lattice rather than individual monomers or capsomers. Among these, Myxovirus resistance protein B (MxB) is a key cellular restriction factor that binds the capsid via its N-terminal fragment containing an arginine-rich motif (RRR), blocking HIV-1 infection at early infection stages. However, the structural basis of this interaction has remained elusive. Here, we present a structural characterization of the CA lattice in complex with the MxB N-terminal fragment using cryo-electron tomography and subtomogram averaging. Combining cryoEM structures with EM-guided all-atom molecular dynamics simulations, we identify residue-specific interactions between MxB and the CA trimer interfaces. Notably, residues 10-20 of the MxB N-terminus adopt an α-helical conformation that stabilizes binding at the CA trimer interface, revealing a distinct mode of capsid engagement. These findings provide insight into arginine-rich motif–mediated recognition by MxB and other host factors and establish a structural framework for the development of capsid-targeting antiviral therapeutics.
SN - 2041-1723
ER -