title: Solution properties of murine leukemia virus gag protein: differences from HIV-1 gag.
abstract: Immature retrovirus particles are assembled from the multidomain Gag protein. In these particles, the Gag proteins are arranged radially as elongated rods. We have previously characterized the properties of HIV-1 Gag in solution. In the absence of nucleic acid, HIV-1 Gag displays moderately weak interprotein interactions, existing in monomer-dimer equilibrium. Neutron scattering and hydrodynamic studies suggest that the protein is compact, and biochemical studies indicate that the two ends can approach close in three-dimensional space, implying the need for a significant conformational change during assembly. We now describe the properties of the Gag protein of Moloney murine leukemia virus (MLV), a gammaretrovirus. We found that this protein is very different from HIV-1 Gag: it has much weaker protein-protein interaction and is predominantly monomeric in solution. This has allowed us to study the protein by small-angle X-ray scattering and to build a low-resolution molecular envelope for the protein. We found that MLV Gag is extended in solution, with an axial ratio of ∼7, comparable to its dimensions in immature particles. Mutational analysis suggests that runs of prolines in its matrix and p12 domains and the highly charged stretch at the C terminus of its capsid domain all contribute to this extended conformation. These differences between MLV Gag and HIV-1 Gag and their implications for retroviral assembly are discussed.
authors.affiliation: HIV Drug Resistance Program, National Cancer Institute-Frederick, P.O. Box B, Frederick, MD 21702-1201, USA. dattasi@mail.nih.gov
authors.forename: Siddhartha A K
authors.initials: SA
authors.lastname: Datta
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zuo
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Clark
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Campbell
authors.forename: Yun-Xing
authors.initials: YX
authors.lastname: Wang
authors.forename: Alan
authors.initials: A
authors.lastname: Rein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D012996:Solutions
chemical_list: D015683:Gene Products, gag; D012996:Solutions