A statistical investigation of amphiphilic properties of C-terminally anchored peptidases.
A number of DD-peptidases have been reported to interact with the membrane via C-terminal amphiphilic alpha-helices, but experimental support for this rests with a few well-characterized cases. These show the C-terminal interactions of DD-carboxypeptidases to involve high levels of membrane penetration, DD-endopeptidases to involve membrane surface binding and class C penicillin-binding proteins to involve membrane binding with intermediate properties. Here, we have characterized C-terminal alpha-helices from each of these peptidase groups according to their amphiphilicity, as measured by mean <microH>, and the corresponding mean hydrophobicity, <H>. Regression and statistical analyses showed these properties to exhibit parallel negative linear relationships, which resulted from the spatial ordering of alpha-helix amino acid residues. Taken with the results of compositional and graphical analyses, our results suggest that the use of C-terminal alpha-helices may be a universal feature of the membrane anchoring for each of these groups of DD-peptidases. Moreover, to accommodate differences between these mechanisms, each group of C-terminal alpha-helices optimizes its structural amphiphilicity and hydrophobicity to fulfil its individual membrane-anchoring function. Our results also show that each anchor type analysed requires a similar overall balance between amphiphilicity for membrane interaction, which we propose is necessary to stabilize their initial membrane associations. In addition, we present a methodology for the prediction of C-terminal alpha-helical anchors from the classes of DD-peptidases analysed, based on a parallel linear model.
Department of Physics, Astronomy and Mathematics, University of Central Lancashire, Preston, PR1 2HE, UK.
James
J
Wallace
Frederick
F
Harris
David A
DA
Phoenix
D000595:Amino Acid Sequence; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry / Q000145:classification; D003198:Computer Simulation; D030562:Databases, Protein; D004789:Enzyme Activation; D016014:Linear Models; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000145:classification*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein / Q000379:methods*; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry* / Q000145:classification*
D008565:Membrane Proteins; D013501:Surface-Active Agents; D002268:Carboxypeptidases; D010447:Peptide Hydrolases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase