Theoretical conformational analysis of the tandem repeat sequence in RNA polymerase II

The largest subunit of RNA polymerase II has an interesting C-terminal doma in, which consists of a multiple tandem repeat of a heptapeptide with the c onsensus sequence Ser-Pro-Thr-Ser-Pro-Ser-Tyr. However, the functional role of this sequence is unclear. One might assume that the conformation of the tandem repeat is very important for its function. A theoretical conformati onal analysis based on molecular mechanics using the energy functions of EC EPP was carried out for a heptapeptide in the repeating unit (Ac-Ser-Pro-Th r-Ser-Pro-Ser-Tyr-NHMe) and a periodic polyheptapeptide corresponding to th e tandem repeat sequence (Ac-(Ser-Pro-Thr-Ser-Pro-Ser-fyr)(16)-NHMe). The m inimum conformations of Ac-Ser-Pro-Thr-Ser-Pro-Ser-Fyr-NHMe had two turn st ructures, an open turn at Pro(2)-Thr(3) and a gamma -turn at Pro(5). The co ntiguous residues to the turns are extended or semi-extended conformations. The low-energy conformations of Ac-(Ser-Pro-Thr-Ser-Pro-Ser-Tyr)(16)-NHMe were long-periodic helices with a large number of residues per turn. Their helical radiuses are approximately 10-13 Angstrom. They mostly have tyrosyl side-chains at the helical interior. They are composed of alternative back bone conformations, which are extended and turn structures, patterned on th e feature of the low-energy conformations of Ac-Ser-Pro-Thr-Ser-Pro-Ser-Tyr -NHMe. It was shown that the long-periodic helices contain turn structures as possible conformations of the C-terminal domain.