Design and Characterization of Peptides That Target Transmembrane Helices

Transmembrane (TM) helices play essential roles in biological processes such as signal transduction, solute transport and membrane protein folding and stability. In order to examine these processes in greater detail, we developed a computational method, CHAMP (computed anti-helical membrane protein), to design peptides which target the TM domains of membrane proteins in a sequence-specific manner. In particular, we designed peptides that target the TM domains of integrins α_IIb and α_ν and demonstrate their specificity in bacterial membrane, platelets and micelles. Furthermore, using genetic selection methods, we are able to examine the specificity and affinity of interactions between the designed and target TM helices. Overall, our results indicate that TM peptides can be designed to selectively activate a given integrin TM domain as well as how a CHAMP methodology can be generalized to examine a wide range of TM-mediated processes.