Protein Classification

Proteins today are very diverse and ordering them into a taxonomy based on natural descent (homology), akin to the taxonomy of organisms, would be of great benefit. Current classification schemes often include analogous traits and lack hierarchical depth. It is tempting, but unfortunately not possible, to extend the taxonomy of organisms to their constituent proteins because proteins, or rather the genes encoding them, are no more tied to an organism than organisms are to an ecosystem. Thus, many genetic events (displacement, duplication, lateral transfer) cause protein phylogenies to differ from those of their parent organisms. For a classification of proteins by descent it is therefore necessary to proceed from their similarity in sequence and structure. Problems arise in detecting this similarity, in interpreting it phylogenetically, in coordinating taxonomic levels (subfamily, family, superfamily, clan) across proteins with vastly different evolutionary histories, and in handling the huge number of proteins in need of classification. We have started to address these problems at several levels, using a few large groups of proteins (AAA ATPases [4], histidine kinases [3] and bacterial surface proteins) as model systems. Our efforts in this area are split between providing detailed and comprehensive phylogenies for individual protein groups (for example [3]) and developing new bioinformatic tools [5].

Fig. 2. Evolution of the double-psi barrel. The figure shows a phylogenetic reconstruction with the main postulated events marked along the branches and, where known, the fold of a protein and its topology (arrows: b-strands, rectangles: a-helices). The existence and nature of the ancestral element that gave rise to this protein superfamily is currently being investigated in our department.


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

[2] Coles M, Diercks T, Liermann J, Groger A, Rockel B, Baumeister W, Koretke KK, Lupas A, Peters J, Kessler H. (1999). The solution structure of VAT-N reveals a 'missing link' in the evolution of complex enzymes from a simple babb element. Curr Biol. 9:1158-1168.

[3] Koretke KK, Volker C, Bower MJ, Lupas AN. (2003). Molecular evolution of histidine kinases. In “Histidine Kinases” (M. Inouye and R. Dutta, eds.), Academic Press.

[4] Lupas AN, Martin J. (2002). AAA proteins. Curr Opin Struct Biol. 12:746-753.

[5] Koretke KK, Russell RB, Lupas AN. (2002). Fold recognition without folds. Protein Sci. 11:1575-1579.