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TitleStructure of native HIV-1 cores and their interactions with IP6 and CypA.
Journal, issue, pagesSci Adv, Vol. 7, Issue 47, Page eabj5715, Year 2021
Publish dateNov 19, 2021
AuthorsTao Ni / Yanan Zhu / Zhengyi Yang / Chaoyi Xu / Yuriy Chaban / Tanya Nesterova / Jiying Ning / Till Böcking / Michael W Parker / Christina Monnie / Jinwoo Ahn / Juan R Perilla / Peijun Zhang /
PubMed AbstractThe 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 ...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.
External linksSci Adv / PubMed:34797722 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution5.4 - 11.5 Å
Structure data

EMDB-12452:
The cryoEM density map hexamer from PFO perforated VLPs in apo state
Method: EM (subtomogram averaging) / Resolution: 5.8 Å

EMDB-12454:
The cryoEM density map hexamer from PFO perforated VLPs in the presence of IP6/CypA
Method: EM (subtomogram averaging) / Resolution: 6.2 Å

EMDB-12455:
The cryoEM density map hexamer from PFO perforated VLPs in the presence of IP6/CypA-DsRed
Method: EM (subtomogram averaging) / Resolution: 6.6 Å

EMDB-12456:
The cryoEM density map pentamer from PFO perforated VLPs
Method: EM (subtomogram averaging) / Resolution: 8.6 Å

EMDB-12457:
The cryoEM density map pentamer from PFO perforated VLPs in the presence of IP6/CypA
Method: EM (subtomogram averaging) / Resolution: 8.7 Å

EMDB-12458:
The cryoEM density map pentamer from PFO perorated VLPs in the presence of IP6/CypA-DsRed
Method: EM (subtomogram averaging) / Resolution: 8.3 Å

EMDB-12459:
The cryoEM density map of hexamer CypA-DsRed binding mode with Two-CypA
Method: EM (subtomogram averaging) / Resolution: 9.4 Å

EMDB-12460:
The cryoEM density map of CA hexamers CypA-DsRed binding mode with one-CypA
Method: EM (subtomogram averaging) / Resolution: 11.5 Å

EMDB-13422:
The cryoEM density map pentamer from PFO perforated VLPs in presence of IP6
Method: EM (subtomogram averaging) / Resolution: 7.2 Å

EMDB-13423:
The cryoEM density map hexamer from PFO perforated VLPs in presence of IP6
Method: EM (subtomogram averaging) / Resolution: 5.4 Å

Source
  • Human immunodeficiency virus 1

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