STRUCTURE DETERMINATION OF THE SMALL UBIQUITIN-RELATED MODIFIER SUMO-1

The recently discovered small ubiquitin-related modifier SUMO-1 belong s to the growing family of ubiquitin-related proteins involved in post ranslational protein modification. Unlike ubiquitin, SUMO-1 does not a ppear to target proteins for degradation but seems to be involved in t he modulation of protein-protein interactions. Independent studies dem onstrate an essential function of SUMO-1 in the regulation of nucleo-c ytoplasmic transport, and suggest a role in cell-cycle regulation and apoptosis. Here, we present the first three-dimensional structure of S UMO-1 solved by NMR. Although having only 18% amino acid sequence iden tity with ubiquitin, the overall structure closely resembles that of u biquitin, featuring the beta beta alpha beta alpha beta fold of the ub iquitin protein family. In addition, the position of the two C-termina l Gly residues required for isopeptide bond formation is conserved bet ween ubiquitin and SUMO-1. The most prominent feature of SUMO-1 is a l ong and highly flexible N terminus, which protrudes from the core of t he protein and which is absent in ubiquitin. Furthermore, ubiquitin Ly s48, required to generate ubiquitin polymers, is substituted in SUMO-1 by Gln69 at the same position, which provides an explanation of why S UMO-1 has not been observed to form polymers. Moreover, the hydrophobi c core of SUMO-1 and ubiquitin is maintained by conserved hydrophobic residues, whereas the overall charge topology of SUMO-1 and ubiquitin differs significantly, suggesting specific modifying enzymes and targe t proteins for both proteins. (C) 1998 Academic Press.