title: Helix perturbations in membrane proteins assist in inter-helical interactions and optimal helix positioning in the bilayer.
abstract: Transmembrane (TM) helices in integral membrane proteins are primarily α-helical in structure. Here we analyze 1134 TM helices in 90 high resolution membrane proteins and find that apart from the widely prevalent α-helices, TM regions also contain stretches of 310(3 to 8 residues) and π-helices (5 to 19 residues) with distinct sequence signatures. The various helix perturbations in TM regions comprise of helices with kinked geometry, as well as those with an interspersed 310/π-helical fragment and show high occurrence in a few membrane proteins. Proline is frequently present at sites of these perturbations, but it is neither a necessary nor a sufficient requirement. Helix perturbations are also conserved within a family of membrane proteins despite low sequence identity in the perturbed region. Furthermore, a perturbation influences the geometry of the TM helix, mediates inter-helical interactions within and across protein chains and avoids hydrophobic mismatch of the helix termini with the bilayer. An analysis of π-helices in the TM regions of the heme copper oxidase superfamily shows that interspersed π-helices can vary in length from 6 to 19 amino acids or be entirely absent, depending upon the protein function. The results presented here would be helpful for prediction of 310and π-helices in TM regions and can assist the computational design of membrane proteins.
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, Karnataka, India.
authors: Ashish
authors: A
authors: Shelar
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, Karnataka, India. Electronic address: mb@mbu.iisc.ernet.in.
authors: Manju
authors: M
authors: Bansal
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D030562:Databases, Protein; D006420:Hemeproteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D010088:Oxidoreductases / Q000737:chemistry*; D011392:Proline / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D017433:Protein Structure, Secondary
chemical_list: D006420:Hemeproteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; D011392:Proline; D010088:Oxidoreductases; C024748:copper oxidase
keywords: 3(10)-Helix; Helix design; Helix kink; Hydrophobic mismatch; Membrane protein modelling; π-Helix