A fast method for the quantitative estimation of the distribution of hydrophobic and hydrophilic segments in alpha-helices of membrane proteins.
The work presents a fast quantitative approach for estimating the orientations of hydrophilic and hydrophobic regions in the helical wheels of membrane-spanning alpha-helices of transmembrane proteins. The common hydropathy analysis provides an estimate of the integral hydrophobicity in a moving window which scans an amino acid sequence. The new parameter, orientation hydrophobicity, is based on the estimate of hydrophobicity of the angular segment that scans the helical wheel of a given amino acid sequence. The corresponding procedure involves the treatment of transmembrane helices as cylinders with equal surface elements for each amino acid residue. The orientation hydrophobicity, P(phi), phi = 0-360 degrees, of a helical cylinder is given as a sum of hydrophobicities of individual amino acids which are taken as the S-shaped functions of the angle between the centre of amino acid surface element and the centre of the segment. Non-zero contribution to P(phi) comes only from the amino acids belonging to the angular segment for a given angle phi. The size of the angular segment is related to the size of the channel pore. The amplitudes of amino acid S-functions are calibrated in the way that their maximum values (reached when the amino acid is completely exposed into the pore) are equal to the corresponding hydropathy index in the selected scale (here taken as Goldman-Engelman-Steitz hydropathy scale). The given procedure is applied in the studies of three ionic channels with well characterized three-dimensional structures where the channel pore is formed by a bundle of alpha-helices: cholera toxin B, nicotinic acetylcholine homopentameric alpha7 receptor, and phospholamban. The estimated maximum of hydrophilic properties at the helical wheels are in a good agreement with the spatial orientations of alpha-helices in the corresponding channel pores.
Luzhkov
V B
VB
Institute of Chemical Physics Problems in Chernogolovka, Russian Academy of Sciences, Chernogolovka, Moscow Region. luzhkov@icp.ac.ru
Surkov
N F
NF
D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002772:Cholera Toxin / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011950:Receptors, Cholinergic / Q000737:chemistry*; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D002772:Cholera Toxin; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D000099211:Phospholamban