Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

Ancestral Module of TIM Barrel Protein Fold

As it has been recently found (1) globular proteins could be considered as assemblies of closed loops of size about 25-35 amino acids. This discovery has its foundation in the physics of polypeptide chains and it suggests specific evolutionary and protein folding connections. At the early evolutionary stages, presumably, a limited amount of the ancestral closed loops existed in form of individual molecules, which appear today as structural elements of modern proteins. Their sequences and 3D structures should have suffered significant changes during evolution. However, several strong cases of conservation of the ancestral closed loops with specific sequences and structures have been described (2). They may be detected by both the structure and sequence similarity to prototypes. Previously we have screened large database of prokaryotic protein sequences to detect frequent 25-30 amino acid residue motifs which all turned out to correspond to closed loops.

This study is geared rather to one protein family, and its characterization in terms of the closed loops. For this we have chosen well studied large group of proteins with TIM-barrel fold (3).

By the RMSD comparison we selected structure related groups (RMSD-groups) among the all closed loops with size from 20 to 41 amino acids. Sequence identity within these families is rather pure. We, thus, used two-letter amino acid alphabet based on the molecular evolution of genetic code (4). The codons can be divided into purine-central and pyrimidine-central codons. Correspondingly, all amino acids divide into two types: G-type (G, D, S, E, N, R, K, Q, C, H, Y, and W) and A-type (A, V, P, S, L, T, I, F and M). These two sets have only one amino acid in common (S), since it is encoded by triplets of both types.

Using this 2-letter alphabet description, we have shown that TIM-barrel protein fold descended from a few basic closed loop prototypes. Moreover, comparison of the main prototype families showed that most probably, they descended from one prototype closed loop of 28 amino acids with four turns of α-helix in the middle.

References and Footnotes
  1. Berezovsky, I. N., Grosberg, A. Y., and Trifonov, E. N. FEBS Lett. 466, 283-286 (2000).
  2. Berezovsky, I. N., Kirzhner, V. M., Kirzhner, A., Rosenfeld, V. R., and Trifonov, E. N. Protein Eng. 15, 955-957 (2002).
  3. Nagano, N., Orengo, C. A., and Thornton, J. M. J. Mol. Biol. 321, 741-765 (2002).
  4. Trifonov, E. N., Kirzhner, A., Kirzhner, V. M., and Berezovsky, I. N. J. Mol. Evol. 53, 394-401 (2001).

Z. M. Frenkel*
E. N. Trifonova

Genome Diversity Center
Institute of Evolution
University of Haifa
Haifa 31905, Israel

*Phone: +972 547 959 406
Email: zfrenkel@yahoo.com
aPhone: +972 4 828 8096
Email: trifonov@research.haifa.ac.il