CONFORMATIONAL STUDY OF THE THR-GLY REPEAT IN THE DROSOPHILA CLOCK PROTEIN, PERIOD

Recent results with the Drosophila melanogaster period gene suggest th at the apparently conserved repetitive motif (Thr-Gly)(n) encoded by t his gene may play an important role in the temperature compensation of the circadian clock. We have therefore initiated both a theoretical a nd experimental conformational analysis of (Thr-Gly)(n) peptides. By u sing a build-up method, it is clear that the hexapeptide (Thr-Gly)(3) represents a 'conformational monomer' and generates a stable type II o r type III beta-turn. Circular dichroism and nuclear magnetic resonanc e spectra of synthetic (Thr-Gly)(3), and poly(Thr-Gly) peptides reveal ed that these peptides exhibit flexible conformations, especially in m ore polar environments and at higher temperatures. We speculate that t his flexibility may illuminate our understanding of both the molecular mechanism of temperature compensation and the systematic geographical distribution within Europe of the Thr-Gly length polymorphism in D. m elanogaster.