title: Is use of the hydrophobic moment a sound basis for predicting the structure-function relationships of membrane interactive alpha-helices?
abstract: Amphiphilic alpha-helices play a fundamental role in protein membrane association and show a segregation of polar and apolar amino acid residues. Based on correlations between amphiphilic properties and biological function, a number of theoretical approaches have been developed, which quantify alpha-helix amphiphilicity and then attempt to assign function. The most commonly used measure of amphiphilicity is the hydrophobic moment, < microH >, which, when used in conjunction with an alpha-helix's mean hydrophobicity, < H >, has been used to classify membrane interactive amphiphilic alpha-helices as either surface active or transmembrane. Here, the predictive efficacy of plot methodology is reviewed by examining published data, which compare the function of known membrane interactive amphiphilic alpha-helices to that assigned by this methodology. The results of this review are discussed in relation to the reliability of < microH > as a quantifier of alpha-helical amphiphilicity, and the ability of < microH > and < H > to describe alpha-helical structure / function relationships. It is concluded that hydrophobic moment plot methodology is not a generally reliable predictor of alpha-helical structure / function relationships. It appears that the inefficacy of plot methodology is primarily due to the inability of the plot diagram to accommodate the heterogeneity of the alpha-helical classes it attempts to define. However, the predictive efficacy of the methodology appears to be improved if other alpha-helical parameters are also considered when assigning alpha-helical function. It is suggested that the conventional methodology should be seen only as an indicator for the assignation of structure / function relationships, providing a guide to future experimental investigations.
authors.affiliation: Dean's Office, Faculty of Science, University of Central Lancashire, Preston, PR1 2HE, UK. daphoenix@uclan.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Phoenix
authors.forename: Frederick
authors.initials: F
authors.lastname: Harris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002154:Calpain / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006602:Hexosyltransferases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008563:Membrane Lipids / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008563:Membrane Lipids; D026901:Membrane Transport Proteins; D046915:Penicillin-Binding Proteins; D011506:Proteins; C084729:kpsE protein, E coli; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002154:Calpain