title: Basic folded and low-populated locally disordered conformers of SUMO-2 characterized by NMR spectroscopy at varying pressures.
abstract: SUMO proteins, a group of post-translational ubiquitin-like modifiers, have target enzymes (E1 and E2) like other ubiquitin-like modifiers, e.g., ubiquitin and NEDD8, but their physiological roles are quite different. In an effort to determine the characteristic molecular design of ubiquitin-like modifiers, we have investigated the structure of human SUMO-2 in solution not only in its basic folded state but also in its higher-energy state by utilizing standard and variable-pressure NMR spectroscopy, respectively. We have determined average coordinates of the basic folded conformer at ambient pressure, which gives a backbone structure almost identical with those of ubiquitin and NEDD8. We have further investigated conformational fluctuations in a wide conformational space using variable-pressure NMR spectroscopy in the range of 30-3 kbar, by which we find a low-populated ( approximately 2.5%) alternative conformer preferentially disordered in the enzyme-binding segment. The alternative conformer is structurally very close to but markedly different in equilibrium population from those for ubiquitin and NEDD8. These results support our notion that post-translational ubiquitin-like modifiers are evolutionarily designed for function both structurally and thermodynamically in their low-populated, high-energy conformers rather than in their basic folded conformers.
authors: RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan.
authors: Ryo
authors: R
authors: Kitahara
authors: Chenhua
authors: C
authors: Zhao
authors: Kohei
authors: K
authors: Saito
authors: Seizo
authors: S
authors: Koshiba
authors: Makoto
authors: M
authors: Ioune
authors: Takanori
authors: T
authors: Kigawa
authors: Shigeyuki
authors: S
authors: Yokoyama
authors: Kazuyuki
authors: K
authors: Akasaka
mesh_terms: D000595:Amino Acid Sequence; D002247:Carbon Isotopes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins