title: Self-assembly properties of a model RING domain.
abstract: RING domains act in a variety of essential cellular processes but have no general function ascribed to them. Here, we observe that purified arenaviral protein Z, constituted almost entirely by its RING domain, self-assembles in vitro into spherical structures that resemble functional bodies formed by Z in infected cells. By using a variety of biophysical methods we provide a thermodynamic and kinetic framework for the RING-dependent self-assembly of Z. Assembly appears coupled to substantial conformational reorganization and changes in zinc coordination of site II of the RING. Thus, the rate-limiting nature of conformational reorganization observed in the folding of monomeric proteins can also apply to the assembly of macromolecular scaffolds. These studies describe a unique mechanism of nonfibrillar homogeneous self-assembly and suggest a general function of RINGs in the formation of macromolecular scaffolds that are positioned to integrate biochemical processes in cells.
authors.affiliation: Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Kentsis
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gordon
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Borden
mesh_terms: D000595:Amino Acid Sequence; D007700:Kinetics; D007836:Lassa virus / Q000737:chemistry / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry / Q000235:genetics; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure
chemical_list: D046911:Macromolecular Substances; D014764:Viral Proteins