SUMO proteins, a group of post-translational ubiquitin-like modifiers, have target enzymes (E1l 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 (∼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.
|Number of pages||10|
|Publication status||Published - 2008 Jan 8|
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