1. Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer.
- Author
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Obr M, Ricana CL, Nikulin N, Feathers JR, Klanschnig M, Thader A, Johnson MC, Vogt VM, Schur FKM, and Dick RA
- Subjects
- Capsid metabolism, Capsid Proteins isolation & purification, Capsid Proteins ultrastructure, Cryoelectron Microscopy, Electron Microscope Tomography, Gene Knockout Techniques, HEK293 Cells, Humans, Models, Molecular, Phosphotransferases (Alcohol Group Acceptor) genetics, Phosphotransferases (Alcohol Group Acceptor) metabolism, Protein Multimerization, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Recombinant Proteins ultrastructure, Rous sarcoma virus pathogenicity, Rous sarcoma virus physiology, Single Molecule Imaging, Transfection, Virus Release, Capsid ultrastructure, Capsid Proteins metabolism, Phytic Acid metabolism, Rous sarcoma virus ultrastructure, Virus Assembly
- Abstract
Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of Tâ=â1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.
- Published
- 2021
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