Solution structure of Urm1 and its implications for the origin of protein modifiers.
Protein modifiers are involved in diverse biological processes and regulate the activity or function of target proteins by covalently conjugating to them. Although ubiquitin and a number of ubiquitin-like protein modifiers (Ubls) in eukaryotes have been identified, no protein modifier has been found in prokaryotes; thus, their evolutionary origin remains a puzzle. To infer the evolutionary relationships between the protein modifiers and sulfur carrier proteins, we solved the solution NMR structure of the Urm1 (ubiquitin-related modifier-1) protein from Saccharomyces cerevisiae. Both structural comparison and phylogenetic analysis of the ubiquitin superfamily, with emphasis on the Urm1 family, indicate that Urm1 is the unique "molecular fossil" that has the most conserved structural and sequence features of the common ancestor of the entire superfamily. The similarities of 3D structure and hydrophobic and electrostatic surface features between Urm1 and MoaD (molybdopterin synthase small subunit) suggest that they may interact with partners in a similar manner, and similarities between Urm1-Uba4 and MoaD-MoeB establish an evolutionary link between ATP-dependent protein conjugation in eukaryotes and ATP-dependent cofactor sulfuration.
Xu
Junjie
J
Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology, Hefei, Anhui 230026, People's Republic of China.
Zhang
Jiahai
J
Wang
Li
L
Zhou
Jie
J
Huang
Hongda
H
Wu
Jihui
J
Zhong
Yang
Y
Shi
Yunyu
Y
D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics
D029701:Saccharomyces cerevisiae Proteins; C406282:URM1 protein, S cerevisiae