Abstract
Kinks are a structural feature of alpha-helices and many are known to have functional roles. Kinks have previously tended to be defined in a binary fashion. In this paper we have deliberately moved towards defining them on a continuum, which given the unimodal distribution of kink angles is a better description. From this perspective, we examine the conservation of kinks in proteins. We find that kink angles are not generally a conserved property of homologs, pointing either to their not being functionally critical or to their function being related to conformational flexibility. In the latter case, the different structures of homologs are providing snapshots of different conformations. Sequence identity between homologous helices is informative in terms of kink conservation, but almost equally so is the sequence identity of residues in spatial proximity to the kink. In the specific case of proline, which is known to be prevalent in kinked helices, loss of a proline from a kinked helix often also results in the loss of a kink or reduction in its kink angle. We carried out a study of the seven transmembrane helices in the GPCR family and found that changes in kinks could be related both to subfamilies of GPCRs and also, in a particular subfamily, to the binding of agonists or antagonists. These results suggest conformational change upon receptor activation within the GPCR family. We also found correlation between kink angles in different helices, and the possibility of concerted motion could be investigated further by applying our method to molecular dynamics simulations. These observations reinforce the belief that helix kinks are key, functional, flexible points in structures.