Protein Evolution

Proteins are the most complex chemical structures found in nature. They have to fold into complicated three-dimensional structures in order to become active. This poses a particular challenge when it comes to explaining their origin from non-living matter.

To date, efforts to understand protein evolution have focused on domains, independently foldable units from which modern proteins are formed. However, domains themselves are too complex to have evolved de novo in an abiotic environment. We believe that domains arose from the fusion of shorter, non-foldable peptides that evolved as cofactors to support a primitive RNA-based life form (the 'RNA world') [1].

Computergestützt versuchen wir, diesen alten Peptidsatz durch vergleichende Studien mit modernen Proteinen zu rekonstruieren, so wie alte Vokabeln durch vergleichende Studien moderner Sprachen rekonstruiert wurden. Experimentell untersuchen wir, wie die Assoziation von kurzen, nicht faltbaren Peptidketten zu gefalteten Proteinen geführt haben könnte.

In particular, we are interested in the role of repetition, a process known to have been essential for the emergence of complexity in other biological systems. To this end, we have selected several structurally repetitive model proteins (Figs. 1,2) to study using protein biochemistry and structural biology. We are also interested in several less obviously repetitive domains, in particular cradle-loop barrels [2] and β-tent folds [3].

 

References

[1] Söding J., Lupas AN. (2003) More than the sum of their parts: On the evolution of proteins from peptides. Bioessays 25:837-846. PMID: 12938173

[2] Alva V., Koretke KK., Coles M., Lupas AN. (2008) Cradle-loop barrels and the concept of metafolds in protein classification by natural descent. Curr Opin Struct Biol 18(3):358-65. PMID: 18457946

[3] Lupas AN., Zhu H., Korycinski M. (2015) The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the β-tent fold. PLoS Comput Biol 11(1):e1004023
PMID: 25569776

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