MxB N-Terminus Adopts a Stable α-Helix to Engage the HIV-1 Capsid Trimer Interface
- 1University of Oxford
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 alpha-helical conformation that stabilizes binding at the CA trimer interface, revealing a previously unrecognized mode of capsid engagement. These findings provide new 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
@misc{zhu2026nterminus,
title = {{MxB N-Terminus Adopts a Stable α-Helix to Engage the HIV-1 Capsid Trimer Interface}},
author = {Y. Zhu and J. S. Rey and J. Shen and J. R. Perilla and P. Zhang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749210},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749210v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - MxB N-Terminus Adopts a Stable α-Helix to Engage the HIV-1 Capsid Trimer Interface
AU - Y. Zhu
AU - J. S. Rey
AU - J. Shen
AU - J. R. Perilla
AU - P. Zhang
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749210
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749210v1
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 alpha-helical conformation that stabilizes binding at the CA trimer interface, revealing a previously unrecognized mode of capsid engagement. These findings provide new 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.
ER -