310 helices in channels and other membrane proteins

Structures of three potassium channels of the six-trans-membrane (TM) helix type, a ligand-gated channel, and two voltage-gated channels were solved recently by x-ray crystallography (Long et al., 2005a,b, 2007; Clayton et al., 2008). In all three channel structures, the fourth TM segment (the voltage sensor in the voltage-gated channels) of each subunit adopts a 3 10-helical confor-mation over an unusually large stretch of residues (7–11 residues). There are still many aspects of the voltage-sensing mechanism that are not understood (Tombola et al., 2006; Swartz, 2008); however, the presence of a 3 10 conformation in the voltage sensor could provide a simple unifying explanation for many aspects of voltage sensing. Here, we present some of the properties of 3 10 helices and discuss these properties within the structural and functional context of potassium channels and of membrane proteins. 3 10 versus  helices The fundamental difference between a 3 10 helix and an  helix is how the backbone hydrogen-bonding network of the two helices is established (Fig. 1). In  helices, the carbonyl group of residue i interacts with the nitrogen from the amide group in residue i+4. Canonical  helices have the following characteristics: 3.6 residues per turn, so that consecutive residues make an angle of 100° around the helical axis, a helical rise per residue of 1.5 Å, and a helical pitch of 5.4 Å. In contrast, in 3 10 helices the carbonyl group in residue i and the nitrogen of the amide group in residue i+3 are hydrogen bonded. Canonical 3 10 helices have three residues per turn, with an angle of 120° between consecutive residues, a helical rise per residue of 1.93–2.0 Å, and a helical pitch of 5.8–6 Å. In very simple terms, a 3 10 helix is more tightly wound, longer, and thinner than an  helix with the same number of residues. Because of their potential functional impact, it is worthwhile focusing our attention on two characteristics of 3 10 helices, stability and dynamics. There is a generalized belief among structural biologists that 3 10 helices are inherently unstable and are, therefore, relatively rare and short, not spanning more than three to four residues. This idea has its origins in the classical studies of the helical conformation of polypeptides. Corey, and Branson proposed the -helical and the 3 10-helical conformations as protein structural motifs, they concluded that the 3 10 helix had a …