title: Domain-swapped dimerization of the HIV-1 capsid C-terminal domain.
abstract: Assembly of the HIV and other retroviruses is primarily driven by the oligomerization of the Gag polyprotein, the major viral structural protein capable of forming virus-like particles even in the absence of all other virally encoded components. Several critical determinants of Gag oligomerization are located in the C-terminal domain of the capsid protein (CA-CTD), which encompasses the most conserved segment in the highly variable Gag protein called the major homology region (MHR). The CA-CTD is thought to function as a dimerization module, although the existing model of CA-CTD dimerization does not readily explain why the conserved residues of the MHR are essential for retroviral assembly. Here we describe an x-ray structure of a distinct domain-swapped variant of the HIV-1 CA-CTD dimer stabilized by a single amino acid deletion. In the domain-swapped structure, the MHR-containing segment forms a major part of the dimerization interface, providing a structural mechanism for the enigmatic function of the MHR in HIV assembly. Our observations suggest that swapping of the MHR segments of adjacent Gag molecules may be a critical intermediate in retroviral assembly.
authors.affiliation: Department of Pathology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA. dmitri.ivanov@hms.harvard.edu
authors.forename: Dmitri
authors.initials: D
authors.lastname: Ivanov
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Tsodikov
authors.forename: Jeremy
authors.initials: J
authors.lastname: Kasanov
authors.forename: Tom
authors.initials: T
authors.lastname: Ellenberger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Tucker
authors.initials: T
authors.lastname: Collins
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D015683:Gene Products, gag / Q000235:genetics*; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D015683:Gene Products, gag