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Structure of native HIV-1 cores and their interactions with IP6 and CypA
The viral capsid plays essential roles in HIV replication and is a major platform engaging host factors. 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 n...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604400/ https://www.ncbi.nlm.nih.gov/pubmed/34797722 http://dx.doi.org/10.1126/sciadv.abj5715 |
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author | Ni, Tao Zhu, Yanan Yang, Zhengyi Xu, Chaoyi Chaban, Yuriy Nesterova, Tanya Ning, Jiying Böcking, Till Parker, Michael W. Monnie, Christina Ahn, Jinwoo Perilla, Juan R. Zhang, Peijun |
author_facet | Ni, Tao Zhu, Yanan Yang, Zhengyi Xu, Chaoyi Chaban, Yuriy Nesterova, Tanya Ning, Jiying Böcking, Till Parker, Michael W. Monnie, Christina Ahn, Jinwoo Perilla, Juan R. Zhang, Peijun |
author_sort | Ni, Tao |
collection | PubMed |
description | The viral capsid plays essential roles in HIV replication and is a major platform engaging host factors. 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. 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. Our structures reveal two IP6 binding sites and modes of cyclophilin A interactions. 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 results demonstrate that perfringolysin O perforation is a valuable tool for structural analyses of enveloped virus capsids and interactions with host cell factors. |
format | Online Article Text |
id | pubmed-8604400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86044002021-12-01 Structure of native HIV-1 cores and their interactions with IP6 and CypA Ni, Tao Zhu, Yanan Yang, Zhengyi Xu, Chaoyi Chaban, Yuriy Nesterova, Tanya Ning, Jiying Böcking, Till Parker, Michael W. Monnie, Christina Ahn, Jinwoo Perilla, Juan R. Zhang, Peijun Sci Adv Biomedicine and Life Sciences The viral capsid plays essential roles in HIV replication and is a major platform engaging host factors. 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. 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. Our structures reveal two IP6 binding sites and modes of cyclophilin A interactions. 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 results demonstrate that perfringolysin O perforation is a valuable tool for structural analyses of enveloped virus capsids and interactions with host cell factors. American Association for the Advancement of Science 2021-11-19 /pmc/articles/PMC8604400/ /pubmed/34797722 http://dx.doi.org/10.1126/sciadv.abj5715 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Ni, Tao Zhu, Yanan Yang, Zhengyi Xu, Chaoyi Chaban, Yuriy Nesterova, Tanya Ning, Jiying Böcking, Till Parker, Michael W. Monnie, Christina Ahn, Jinwoo Perilla, Juan R. Zhang, Peijun Structure of native HIV-1 cores and their interactions with IP6 and CypA |
title | Structure of native HIV-1 cores and their interactions with IP6 and CypA |
title_full | Structure of native HIV-1 cores and their interactions with IP6 and CypA |
title_fullStr | Structure of native HIV-1 cores and their interactions with IP6 and CypA |
title_full_unstemmed | Structure of native HIV-1 cores and their interactions with IP6 and CypA |
title_short | Structure of native HIV-1 cores and their interactions with IP6 and CypA |
title_sort | structure of native hiv-1 cores and their interactions with ip6 and cypa |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604400/ https://www.ncbi.nlm.nih.gov/pubmed/34797722 http://dx.doi.org/10.1126/sciadv.abj5715 |
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