Evolution and design of protein folds

In order to understand protein function it is important to understand how the specific and efficient contemporary enzymes evolved from less specific and less efficient precursors. The evolution of the frequently encountered (βα)8-barrel fold and its relationship to other folds such as the flavodoxin-like proteins is used to investigate this question. The enzymes HisA, HisF as well as many related (βα)8-barrel enzymes are believed to have evolved from a precursor half its size, namely from (βα)4-half-barrel domains. Database searches have revealed striking structural similarities between half-barrels and proteins adopting the flavodoxin-like (βα)5-fold. The analysis of the relationship between these structurally similar protein folds is the topic of this project. Its aim is to learn about evolutionary mechanisms that allow for the adaptation of new protein folds.

Webcast on this topic

based on the presentation entitled 'Engineering proteins from fold fragments' presented at the joint Biochemical Society / Protein Society Focused Meeting 'Protein engineering: new approaches and applications', held in April 2013. [BiochemSociety]

Selected References:

Farias-Rico, J.A., Schmidt, S. & Höcker, B. (2014) Evolutionary relationship of two ancient protein superfolds. Nature Chem Biol doi:10.1038/nchembio.1579.


Eisenbeis, S., Proffitt, W., Coles, M., Truffault, V., Shanmugaratnam, S., Meiler, J. & Höcker, B. (2012) The potential of fragment recombination for the rational design of proteins. J Am Chem Soc 134, 4019-22. [PubMed]

Schreier, B. & Höcker, B. (2010) Engineering the enolase magnesium II binding site: implications for its evolution. Biochem 49, 7582-9. [PubMed]

Bharat, T.A.M., Eisenbeis, S., Zeth, K. & Höcker, B. (2008) A βα-barrel built by the combination of fragments from different folds. Proc Natl Acad Sci U S A 105, 9942-7. [PubMed]

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