The closed loops within the proteins of the TIM-barrel fold family are analyzed and compared sequence- and structure-wise. The size distribution of the closed loops of the TIM-barrels confirms universal preference to the standard size of 25-30 residues. 3D structural RMSD comparisons of the closed loops and presentation of their sequences in binary form suggest that the TIM-barrel proteins are built from descendants of several types of basic closed loop prototypes. Comparison of these prototypes points to a likely common ancestor -- the alpha helix containing closed loops of 28 amino acids. The presumed ancestor is characterized by specific binary consensus sequence.

Key words: Sequence/structure prototype, Closed loops, Protein evolution, TIM barrel.