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TitleArg18 Substitutions Reveal the Capacity of the HIV-1 Capsid Protein for Non-Fullerene Assembly.
Journal, issue, pagesViruses, Vol. 16, Issue 7, Year 2024
Publish dateJun 27, 2024
AuthorsRandall T Schirra / Nayara F B Dos Santos / Barbie K Ganser-Pornillos / Owen Pornillos /
PubMed AbstractIn the fullerene cone HIV-1 capsid, the central channels of the hexameric and pentameric capsomers each contain a ring of arginine (Arg18) residues that perform essential roles in capsid assembly and ...In the fullerene cone HIV-1 capsid, the central channels of the hexameric and pentameric capsomers each contain a ring of arginine (Arg18) residues that perform essential roles in capsid assembly and function. In both the hexamer and pentamer, the Arg18 rings coordinate inositol hexakisphosphate, an assembly and stability factor for the capsid. Previously, it was shown that amino-acid substitutions of Arg18 can promote pentamer incorporation into capsid-like particles (CLPs) that spontaneously assemble in vitro under high-salt conditions. Here, we show that these Arg18 mutant CLPs contain a non-canonical pentamer conformation and distinct lattice characteristics that do not follow the fullerene geometry of retroviral capsids. The Arg18 mutant pentamers resemble the hexamer in intra-oligomeric contacts and form a unique tetramer-of-pentamers that allows for incorporation of an octahedral vertex with a cross-shaped opening in the hexagonal capsid lattice. Our findings highlight an unexpected degree of structural plasticity in HIV-1 capsid assembly.
External linksViruses / PubMed:39066201 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 7.1 Å
Structure data

EMDB-43632: HIV-1 CA R18L tetramer-of-pentamers
Method: EM (single particle) / Resolution: 5.8 Å

EMDB-43633: HIV-1 CA R18L single-pentamer declination
Method: EM (single particle) / Resolution: 6.6 Å

EMDB-43634: HIV-1 CA R18A tetramer-of-pentamers
Method: EM (single particle) / Resolution: 6.0 Å

EMDB-43635: HIV-1 CA R18G tetramer-of-pentamers
Method: EM (single particle) / Resolution: 7.1 Å

EMDB-43636: HIV-1 CA R18L capsid-like particle assembled in 1 M NaCl bound to FG-peptide
Method: EM (single particle) / Resolution: 5.3 Å

EMDB-43637: HIV-1 CA R18L capsid-like particle assembled with FG-peptide
Method: EM (single particle) / Resolution: 5.4 Å

EMDB-43638: HIV-1 CA R18L octahedron assembled with FG-peptide
Method: EM (single particle) / Resolution: 4.0 Å

43641

8vxv

EMDB-43641, PDB-8vxv:
HIV-1 R18L CA hexamer
Method: EM (single particle) / Resolution: 3.7 Å

43642

8vxw

EMDB-43642, PDB-8vxw:
HIV-1 R18L CA pentamer from capsid-like particles assembled in 1 M NaCl
Method: EM (single particle) / Resolution: 4.4 Å

Source
  • human immunodeficiency virus 1
  • Homo sapiens (human)
KeywordsVIRUS LIKE PARTICLE / capsid

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