engleski

Hydrophobic moments of voltage sensors in cation channels

Voltage-gated channels are one of the most important classes of integral membrane proteins. Many of these proteins have similar overall architecture and essentially the same voltage-sensing mechanism. They exhibit approximate fourfold symmetry in which each subunit or domain contains an S4 voltage sensor and five hydrophobic segments. The S4 segment is highly positively charged, arginine or lysine residue are present nearly every third position (after one arginine or lysine), and therefore difficult to detect with standard methods for prediction of transmembrane domains. We propose hydrophobic moment (HM) as a new descriptor for S4 segments in addition to homology. Hydrophobic moments are functions of residues hydrophobicity and periodicity of three-dimensional structure. Standard inputs for calculation of HM are Eisenberg hydrophobic scale, period of 3.6 (alpha-helix) and window length of 11 residues. The training data set consists of 120 proteins (13 sodium, 41 calcium and 66 potassium channels) with thoroughly checked annotation of S4 segments. We calculated moments for 92 scales and chose the scales that had maximal HM for S4 segments. The best scales were scales reported by Jacob and White[1]. This calculation highlighted the importance of the scale selection. Detection of specific patterns in protein sequence based on profiles (or functions, as in this case) of hydrophobicity, preferences or other residues attributes can vary much with scale selection. As an example we show that profiles of HM calculated with dissimilar scales differ significantly. The S4 segments of four repeating units of the sodium and calcium channels show similar arrangement: the each third segment has the highest HM, while moments of the first and second segments are almost equal. Hydrophobic moments of potassium channels grouped according to the previously known classification. These results confirm that hydrophobic moments with specific scale selection are very good descriptors of S4 segments for various classes of voltage-gated channels. The connection of conservation of hydrophobic moments with structure and function of voltage-gated sensors are yet to be investigated.[1]R. Jacobs and S. H. White, The nature of the hydrophobic bonding of small peptides at the bilayer interface: implications for the insertion of transbilayer helices, Biochemistry 28 (1989) 3421-3437

hydrophobic moment; voltage sensors

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