The capsid is organized as a fullerene-like cone, within which about 200 CA hexamers and 12 pentamers make up the conical lattice ( 1– 3). The HIV-1 capsid is made of capsid protein (CA), which contains two separate domains, CA N-terminal domain (CA NTD) and CA C-terminal domain (CA CTD), connected by a flexible linker. It is also a major platform that engages many host dependency and restriction factors via higher-order surface pattern recognition.
The retroviral capsid is a container that encapsulates the viral genome and protects it from host innate immune responses during the early stage of infection. Upon infection, the RNA genome is reverse-transcribed into a double-stranded DNA, which is then integrated into the host genome. Retroviruses are enveloped single-stranded positive-sense RNA viruses. Our results demonstrate that perfringolysin O perforation is a valuable tool for structural analyses of enveloped virus capsids and interactions with host cell factors.
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Free energy calculations substantiate the two binding sites at R18 and K25 and further show a prohibitive energy barrier for IP6 to pass through the pentamer. Our structures reveal two IP6 binding sites and modes of cyclophilin A interactions. Using cryo–electron tomography and subtomogram averaging, we determined the structures of native capsomers in the presence and absence of inositol hexakisphosphate (IP6) and cyclophilin A and constructed an all-atom model of a complete HIV-1 capsid. To overcome challenges in study native capsid structure, we used the perfringolysin O to perforate the membrane of HIV-1 particles, thus allowing host proteins and small molecules to access the native capsid while improving cryo–electron microscopy image quality. The viral capsid plays essential roles in HIV replication and is a major platform engaging host factors. Perilla, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing,Īnd Peijun Zhang, Conceptualization, Data curation, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - review & editing Parker, Conceptualization, Funding acquisition, Resources, Writing - review & editing,Ĭhristina Monnie, Investigation, Resources, Validation, Till Böcking, Funding acquisition, Methodology, Tanya Nesterova, Formal analysis, Software, Yuriy Chaban, Formal analysis, Validation, , † Chaoyi Xu, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - review & editing, , † Zhengyi Yang, Formal analysis, Investigation, Resources, Software, Validation, Writing - original draft, , † Yanan Zhu, Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing, Tao Ni, Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing - original draft, Writing - review & editing,
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