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TitleIntrinsic curvature of the HIV-1 CA hexamer underlies capsid topology and interaction with cyclophilin A.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 9, Page 855-862, Year 2020
Publish dateAug 3, 2020
AuthorsTao Ni / Samuel Gerard / Gongpu Zhao / Kyle Dent / Jiying Ning / Jing Zhou / Jiong Shi / Jordan Anderson-Daniels / Wen Li / Sooin Jang / Alan N Engelman / Christopher Aiken / Peijun Zhang /
PubMed AbstractThe mature retrovirus capsid consists of a variably curved lattice of capsid protein (CA) hexamers and pentamers. High-resolution structures of the curved assembly, or in complex with host factors, ...The mature retrovirus capsid consists of a variably curved lattice of capsid protein (CA) hexamers and pentamers. High-resolution structures of the curved assembly, or in complex with host factors, have not been available. By devising cryo-EM methodologies for exceedingly flexible and pleomorphic assemblies, we have determined cryo-EM structures of apo-CA hexamers and in complex with cyclophilin A (CypA) at near-atomic resolutions. The CA hexamers are intrinsically curved, flexible and asymmetric, revealing the capsomere and not the previously touted dimer or trimer interfaces as the key contributor to capsid curvature. CypA recognizes specific geometries of the curved lattice, simultaneously interacting with three CA protomers from adjacent hexamers via two noncanonical interfaces, thus stabilizing the capsid. By determining multiple structures from various helical symmetries, we further revealed the essential plasticity of the CA molecule, which allows formation of continuously curved conical capsids and the mechanism of capsid pattern sensing by CypA.
External linksNat Struct Mol Biol / PubMed:32747784 / PubMed Central
MethodsEM (helical sym.) / EM (single particle)
Resolution3.5 - 6.9 Å
Structure data

EMDB-10226, PDB-6skk:
Structure of the native full-length HIV-1 capsid protein in helical assembly (-13,8)
Method: EM (helical sym.) / Resolution: 3.6 Å

EMDB-10228, PDB-6skm:
Structure of the native full-length HIV-1 capsid protein A92E in helical assembly (-13,12)
Method: EM (helical sym.) / Resolution: 4.9 Å

EMDB-10229, PDB-6skn:
Structure of the native full-length HIV-1 capsid protein in helical assembly (-13,8)
Method: EM (helical sym.) / Resolution: 4.5 Å

EMDB-10239, PDB-6slq:
Structure of the native full-length HIV-1 capsid protein A92E in helical assembly (-12,11)
Method: EM (helical sym.) / Resolution: 4.4 Å

EMDB-10240, PDB-6slu:
Structure of the native full-length HIV-1 capsid protein A92E in helical assembly (-13,11)
Method: EM (helical sym.) / Resolution: 4.7 Å

EMDB-10246, PDB-6smu:
Structure of the native full-length HIV-1 capsid protein in helical assembly (-13,12)
Method: EM (helical sym.) / Resolution: 5.0 Å

EMDB-10738, PDB-6y9v:
Structure of the native full-length HIV-1 capsid protein in complex with Cyclophilin A from helical assembly (-8,13)
Method: EM (single particle) / Resolution: 6.9 Å

EMDB-10739, PDB-6y9w:
Structure of the native full-length HIV-1 capsid protein in complex with Cyclophilin A from helical assembly (-13,8)
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-10740, PDB-6y9x:
Structure of the native full-length HIV-1 capsid protein in complex with Cyclophilin A from helical assembly (-13,7)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-10741, PDB-6y9y:
Structure of the native full-length HIV-1 capsid protein in complex with Cyclophilin A from helical assembly (-7,13)
Method: EM (single particle) / Resolution: 6.1 Å

EMDB-10742, PDB-6y9z:
Structure of the native full-length HIV-1 capsid protein in complex with Cyclophilin A from helical assembly (-13,9)
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-10816, PDB-6yj5:
Focused refinement cryo-EM structure of the yeast mitochondrial complex I sub-stoichiometric sulfur transferase subunit
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-11176, PDB-6zdj:
Structure of the native full-length HIV-1 capsid protein in complex with Cyclophilin A from helical assembly (-13,10)
Method: EM (single particle) / Resolution: 5.8 Å

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
  • yarrowia lipolytica (yeast)
KeywordsVIRAL PROTEIN / HIV / capsid / hexamer / helical assembly / curvature / TRANSFERASE / NADH:Ubiquinone Oxidoreductase / sulfur transferase / sub-stoichiometric / complex I

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