title: Common semiopen conformations of Mg2+-free Ras, Rho, Rab, Arf, and Ran proteins combined with GDP and their similarity with GEF-bound forms.
abstract: A computational study was performed on the Mg(2+)-free conformations of the small guanine nucleotide-binding proteins (GNBPs): Ras, Rho, Rab, Arf, and Ran, which were complexed with GDP. Molecular dynamics (MD) simulation was executed for each complex for the duration of 3.0 ns to investigate the effects of Mg(2+) ions on the GNBPs' structure. The results indicated that all Mg(2+)-free GNBPs formed a groove between the switch region and the nucleotide-binding site. In some GNBP families, the release of Mg(2+) was reported to play an important role in binding the guanine nucleotide-exchanging factor (GEF) promoting the GDP/GTP exchange reaction. Interestingly, the grooves, which appeared in the MD simulations, were similar to the grooves experimentally observed in the GNBP-GEF complex. We also calculated the Mg(2+)-bound GNBPs to compare with the Mg(2+)-free forms. No groove was observed in the Mg(2+)-bound GNBPs. These results demonstrated a regulatory role of Mg(2+) ion to prepare a template for the GEF binding. Moreover, the results suggested that the release of Mg(2+) ion lead to the GEF-GNBP binding.
authors.affiliation: Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Inage-ku, Chiba 263-8522, Japan. moriken@graduate.chiba-u.jp
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hata
authors.forename: Saburo
authors.initials: S
authors.lastname: Neya
authors.forename: Tyuji
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002413:Cations, Divalent; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006150:Guanine Nucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012997:Solvents / Q000737:chemistry; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D020662:Guanine Nucleotide Exchange Factors; D006150:Guanine Nucleotides; D012997:Solvents; D006153:Guanosine Diphosphate; D019204:GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020931:ran GTP-Binding Protein; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D008274:Magnesium