title: Polar/Ionizable residues in transmembrane segments: effects on helix-helix packing.
abstract: The vast majority of membrane proteins are anchored to biological membranes through hydrophobic α-helices. Sequence analysis of high-resolution membrane protein structures show that ionizable amino acid residues are present in transmembrane (TM) helices, often with a functional and/or structural role. Here, using as scaffold the hydrophobic TM domain of the model membrane protein glycophorin A (GpA), we address the consequences of replacing specific residues by ionizable amino acids on TM helix insertion and packing, both in detergent micelles and in biological membranes. Our findings demonstrate that ionizable residues are stably inserted in hydrophobic environments, and tolerated in the dimerization process when oriented toward the lipid face, emphasizing the complexity of protein-lipid interactions in biological membranes.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Universitat de València, Burjassot, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bañó-Polo
authors.forename: Carlos
authors.initials: C
authors.lastname: Baeza-Delgado
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.forename: Marc A
authors.initials: MA
authors.lastname: Marti-Renom
authors.forename: Concepción
authors.initials: C
authors.lastname: Abad
authors.forename: Ismael
authors.initials: I
authors.lastname: Mingarro
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000252:Calcium-Transporting ATPases / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000378:metabolism; D006021:Glycophorins / Q000737:chemistry; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry*; D008823:Micelles; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D006021:Glycophorins; D008565:Membrane Proteins; D008823:Micelles; D012967:Sodium Dodecyl Sulfate; D000252:Calcium-Transporting ATPases