Retroviral CA subdomains encode their immature assembly properties independently of strict subdomain co-pairing
- 1Institute of Science and Technology Austria (ISTA)
Abstract
Retroviral capsid (CA) proteins display a conserved two-domain architecture consisting of independently folded N-terminal (CA-NTD) and a C-terminal (CA-CTD) subdomains. Despite a strong CA protein fold conservation, different retrovirus species are employing remarkably variable geometrical solutions to stabilize the CA lattices that form the immature virus particle. For instance, while HTLV-1 has been reported to use the CA-NTD to stabilize its immature lattice, HIV-1 relies on a contiguous structural unit formed of the CA-CTD together with the short spacer peptide 1 (SP1). This raises the question whether immature assembly phenotypes are modular features encoded independently into individual CA subdomains, or if they are emergent features requiring strict co-pairing or co-evolution between CA subdomains of a given species. To test for these two options, we have designed chimeric proteins pairing the CA subdomains of HTLV-1 and HIV-1. Our results show that the CA subdomains of HIV-1 and HTLV-1 can be clearly distinguished into assembly-passive and assembly-driving categories. Moreover, pairing assembly-driving subdomains from the two retrovirus species still allows them to independently form their native immature contacts, while at the same time trying to impose their preferred curvature on each other. Mutations of either subdomain within the chimeric context do not disrupt assembly, but rather shift the phenotype balance while relieving curvature strains, demonstrating that all immature assembly properties can be encoded into a single subdomain. Our results therefore highlight that the two-domain architecture of retroviral capsid is a result of a division of labor approach built on structural modularity, where, at least for immature assembly, one of the subdomains is the key driver for assembly competence while the other could serve more regulatory functions.
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BibTeX
@misc{percipalle2026retroviral,
title = {{Retroviral CA subdomains encode their immature assembly properties independently of strict subdomain co-pairing}},
author = {M. Percipalle and A. Thader and V.-V. Hodirnau and R. A. Dick and F. K. Schur},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759032},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759032v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Retroviral CA subdomains encode their immature assembly properties independently of strict subdomain co-pairing
AU - M. Percipalle
AU - A. Thader
AU - V.-V. Hodirnau
AU - R. A. Dick
AU - F. K. Schur
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759032
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759032v1
AB - Retroviral capsid (CA) proteins display a conserved two-domain architecture consisting of independently folded N-terminal (CA-NTD) and a C-terminal (CA-CTD) subdomains. Despite a strong CA protein fold conservation, different retrovirus species are employing remarkably variable geometrical solutions to stabilize the CA lattices that form the immature virus particle. For instance, while HTLV-1 has been reported to use the CA-NTD to stabilize its immature lattice, HIV-1 relies on a contiguous structural unit formed of the CA-CTD together with the short spacer peptide 1 (SP1). This raises the question whether immature assembly phenotypes are modular features encoded independently into individual CA subdomains, or if they are emergent features requiring strict co-pairing or co-evolution between CA subdomains of a given species. To test for these two options, we have designed chimeric proteins pairing the CA subdomains of HTLV-1 and HIV-1. Our results show that the CA subdomains of HIV-1 and HTLV-1 can be clearly distinguished into assembly-passive and assembly-driving categories. Moreover, pairing assembly-driving subdomains from the two retrovirus species still allows them to independently form their native immature contacts, while at the same time trying to impose their preferred curvature on each other. Mutations of either subdomain within the chimeric context do not disrupt assembly, but rather shift the phenotype balance while relieving curvature strains, demonstrating that all immature assembly properties can be encoded into a single subdomain. Our results therefore highlight that the two-domain architecture of retroviral capsid is a result of a division of labor approach built on structural modularity, where, at least for immature assembly, one of the subdomains is the key driver for assembly competence while the other could serve more regulatory functions.
ER -