Hierarchical Folding of Sub-domais coded by Exons and Molten Grobule State of Retinol Binding Protein

Understanding the folding dynamics of tertiary structures is important for protein design and engineering. However, something new information is needed for the further progress of protein research. Comparison between the predicted structures for the partial peptide sequence and the corresponding part of the X-ray structure seemed to show some clue to the information. Here, we uncovered another structural hierarchy of retinol binding protein; most subdomains coded in exons fold independently with extended C-terminals and the latter segment interact with the former folded subdomain to form the final structure. Our result was discussed with Exon Junction Complex and the tunnel structure of ribosome. Furthermore, the structural variability of the subdomain coded in the third exon was suggested to have a unique characteristic. Molecular dynamics of this protein with SDS micelle showed a possible change at the latter half of the third exon, whose secondary structure ratio is consistent with published results of the CD spectrum. Therefore, this conformational change is responsible for the molten globule state of the protein for releasing its ligand to a target cell. Although our result and discussion must be confirmed in another proteins and by experimental study, they should be useful for protein research.