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Solution structure of ThiS and implications for the evolutionary roots of ubiquitin


ThiS is a sulfur carrier protein that plays a central role in thiamin biosynthesis in Escherichia coli. Here we report the solution NMR structure of ThiS, the first for this class of sulfur carrier proteins. Although ThiS shares only 14% sequence identity with ubiquitin, it possesses the ubiquitin fold. This structural homology, combined with established functional similarities involving sulfur chemistry, demonstrates that the eukaryotic ubiquitin and the prokaryotic ThiS evolved from a common ancestor. This illustrates how structure determination is essential in establishing evolutionary links between proteins in which structure and function have been conserved through eons of evolution despite loss of sequence identity. The ThiS structure reveals both hydrophobic and electrostatic surface features that are likely determinants for interactions with binding partners. Comparison with surface features of ubiquitin and ubiquitin homologs SUMO-1, RUB-1 and NEDD8 suggest how Nature has utilized this single fold to incorporate similar chemistry into a broad array of highly specific biological processes.

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Figure 1: Functional similarity between ubiquitin (Ub) and ThiS.
Figure 2: Solution structure determination of ThiS.
Figure 3: Tree of ubiquitin homologs.
Figure 4: Structure-function relationship between ThiS and ubiquitin.

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We thank P.A. Karplus, R.J. MacIntyre, R.E. Oswald and R.-H. Chen for very helpful comments and discussion, L.E. Kay for use of his pulse sequence library, and F. Delaglio and D. Garrett (NIH/NIDDK) for use of their software tools. This research was funded by the NIH and the NSF. C.Wang was supported by a graduate fellowship from the Olin Foundation.

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Correspondence to Linda K. Nicholson.

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Wang, C., Xi, J., Begley, T. et al. Solution structure of ThiS and implications for the evolutionary roots of ubiquitin. Nat Struct Mol Biol 8, 47–51 (2001).

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