Planes formed with four intron-positions in tertiary structures of retinol binding protein and calpain domain VI

Eukaryotic genes have intervening sequences, introns, in their coding regions. Since introns are spliced out from m-RNA before translation, they are considered to have no effect on the protein structure. Here, we report a novel relationship between introns and the tertiary structures of retinol binding protein and calpain domain VI. We identified "intron-positions" as amino acid residues on which or just after which introns are found in their corresponding nucleotide sequences, and then found that four intron-positions form a plane. We also found that the four intron-positions of retinol-binding protein encloses its ligand retinol. The tertiary structure of calpain domain VI changes after Ca(2+) binding, and the four intron-positions form a plane that includes its ligand calpastatin. To evaluate the statistical significance of the planarity, we calculated the mean distance of each intron-position from the plane defined by the other three intron-positions, and showed that it is significantly smaller than the one calculated for randomly generated locations based on exon size distribution. On the basis of this finding, we discuss the evolution of retinol binding protein and the origin of introns.