Non-α-helical elements modulate polytopic membrane protein architecture

In “all α-fold” transmembrane proteins, including ion channels, G-protein-coupled receptors (GPCRs), bacterial rhodopsins and photosynthetic reaction centers, relatively long α-helices, straight, curved or kinked, pack into compact elliptical or circular domains. Using both existing and newly developed tools to analyze transmembrane segments of all available membrane protein three-dimensional structures, including that very recently elucidated for the GPCR, rhodopsin, we report here the finding of frequent non-α-helical components, i.e. 310-helices (“tight turns”), π-helices (“wide turns”) and intrahelical kinks (often due to residues other than proline). Often, diverse helical types and kinks concatenate over long segments and produce complex inclinations of helical axis, and/or diverse frame shifts in the “canonical”, α-helical side-chain pattern. Marked differences in transmembrane architecture exist even between seemingly structurally related proteins, such as bacteriorhodopsin and rhodopsin. Deconvolution of these non-canonical features into their composite elements is essential for understanding the pleiotropy of polytopic protein structure and function, and must be considered in developing valid macromolecular models.