Evolutionary relationship of two ancient protein superfolds

ABSTRACT Proteins are the molecular machines of the cell that fold into specific three-dimensional structures to fulfill their functions. To improve our understanding of how the structure

and function of proteins arises, it is crucial to understand how evolution has generated the structural diversity we observe today. Classically, proteins that adopt different folds are

considered to be nonhomologous. However, using state-of-the-art tools for homology detection, we found evidence of homology between proteins of two ancient and highly populated protein

folds, the (βα)8-barrel and the flavodoxin-like fold. We detected a family of sequences that show intermediate features between both folds and determined what is to our knowledge the first

representative crystal structure of one of its members, giving new insights into the evolutionary link of two of the earliest folds. Our findings contribute to an emergent vision where

protein superfolds share common ancestry and encourage further approaches to complete the mapping of structure space onto sequence space. Access through your institution Buy or subscribe

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for molecular graphics. _Acta Crystallogr. D Biol. Crystallogr._ 60, 2126–2132 (2004). PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank S. Toledo-Patiño, V. Alva and J.

Söding for discussions. We are grateful to the crystallography community at the Max Planck Institute for their support. This work was supported by Deutsche Forschungsgemeinschaft grant HO

4022/1-2. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Max Planck Institute for Developmental Biology, Tübingen, Germany José Arcadio Farías-Rico, Steffen Schmidt & Birte Höcker Authors

* José Arcadio Farías-Rico View author publications You can also search for this author inPubMed Google Scholar * Steffen Schmidt View author publications You can also search for this

author inPubMed Google Scholar * Birte Höcker View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS J.A.F.-R. and B.H. designed the research;

J.A.F.-R. performed the experiments; J.A.F.-R., S.S. and B.H. analyzed the data; and J.A.F.-R. and B.H. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Birte Höcker. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Results, Supplementary Figures

1–7 and Supplementary Tables 1 and 2. (PDF 13146 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Farías-Rico, J., Schmidt, S. & Höcker, B.

Evolutionary relationship of two ancient protein superfolds. _Nat Chem Biol_ 10, 710–715 (2014). https://doi.org/10.1038/nchembio.1579 Download citation * Received: 13 March 2014 * Accepted:

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