Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V40
Höfundar / Authors: Stefán R. Jónsson (1), Fidel Jr. Arizaga (2), Yong Xiong (2)
Starfsvettvangur / Affiliations: 1. Institute for Experimental Pathology, University of Iceland, Keldur, 2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut
Kynnir / Presenter: Stefán Ragnar Jónsson
Lentiviruses require a mature capsid to package and traffic their viral genome for successful infection and propagation. Although the HIV-1 capsid structure has been extensively studied, structural information is lacking for other lentiviral capsids, limiting our understanding. Using cryo-EM and the CA liposome-templating system, we assembled CLPs and solved the pentamer and hexamer structures for the two major phylogenetic groups of SRLVs: MVV and CAEV. The results reveal differences between the SRLVs and the HIV-1 CA lattice assemblies. SRLV CLPs have a propensity to form a flatter surface compared to those of HIV-1. Additionally, CA molecules in SRLV pentamers adopt a distinct NTD orientation compared to that of the HIV-1 pentamers. Both SRLV CA pentamers and hexamers lack IP6 at their central pores, a feature critical for HIV-1. Taken together, these observations paired with our molecular dynamics (MD) simulation results suggest a potentially distinct mechanism for importing dNTP molecules into SRLV capsids. Key regions of HIV-1 CA-host factor interaction, such as the CypA-binding motifs, have diverged in the SRLV CA systems. Our results have revealed important features unique to the SRLV lentiviral capsids, which may facilitate structure based inhibitor design strategies.