Visualization of a missing link in retrovirus capsid assembly.
For a retrovirus such as HIV to be infectious, a properly formed capsid is needed; however, unusually among viruses, retrovirus capsids are highly variable in structure. According to the fullerene conjecture, they are composed of hexamers and pentamers of capsid protein (CA), with the shape of a capsid varying according to how the twelve pentamers are distributed and its size depending on the number of hexamers. Hexamers have been studied in planar and tubular arrays, but the predicted pentamers have not been observed. Here we report cryo-electron microscopic analyses of two in-vitro-assembled capsids of Rous sarcoma virus. Both are icosahedrally symmetric: one is composed of 12 pentamers, and the other of 12 pentamers and 20 hexamers. Fitting of atomic models of the two CA domains into the reconstructions shows three distinct inter-subunit interactions. These observations substantiate the fullerene conjecture, show how pentamers are accommodated at vertices, support the inference that nucleation is a crucial morphologic determinant, and imply that electrostatic interactions govern the differential assembly of pentamers and hexamers.
Cardone
Giovanni
G
Laboratory of Structural Biology, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Purdy
John G
JG
Cheng
Naiqian
N
Craven
Rebecca C
RC
Steven
Alasdair C
AC
D002213:Capsid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D006678:HIV / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation; D011110:Polymorphism, Genetic; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D052736:Rous sarcoma virus / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D055672:Static Electricity; D019065:Virus Assembly
D036022:Capsid Proteins; D050505:Mutant Proteins; D021122:Protein Subunits