Harnessing the unique structural properties of isolated {alpha}-helices [Protein Structure and Folding]

July 24th, 2014 by Swanson, C. J., Sivaramakrishnan, S.

The α-helix is a ubiquitous secondary structural element that is almost exclusively observed in proteins when stabilized by tertiary or quaternary interactions. However, beginning with the unexpected observations of α-helix formation in the isolated C-peptide in ribonuclease A, there is growing evidence that a significant percentage (0.2 %) of all proteins contain isolated stable single α-helical domains (SAH). These SAH domains provide unique structural features essential for normal protein function. A subset of SAH domains contain a characteristic ER/K motif, comprised of a repeating sequence of ~ four consecutive glutamic acids (E) followed by ~ four consecutive basic arginine or lysine (R/K) residues. The ER/K α-helix, also termed the ER/K linker, has been extensively characterized in the context of the myosin family of molecular motors, and is emerging as a versatile structural element for protein and cellular engineering applications. Here, we review the structure and function of SAH domains, and the tools to identify them in natural proteins. We conclude with a discussion of recent studies that have successfully used the modular ER/K linker for engineering chimeric myosin proteins with altered mechanical properties, as well as synthetic polypeptides that can be used to monitor and systematically modulate protein interactions within cells.