title: Changes in transmembrane helix alignment by arginine residues revealed by solid-state NMR experiments and coarse-grained MD simulations.
abstract: Independent experimental and computational approaches show agreement concerning arginine/membrane interactions when a single arginine is introduced at selected positions within the membrane-spanning region of acetyl-GGALW(5)LALALAL(12)AL(14)ALALW(19)LAGA-ethanolamide, designated GWALP23. Peptide sequence isomers having Arg in position 12 or position 14 display markedly different behaviors, as deduced by both solid-state NMR experiments and coarse-grained molecular dynamics (CG-MD) simulations. With respect to the membrane normal of DOPC or DPPC lipid bilayer membranes, GWALP23-R14 shows one major state whose apparent average tilt is approximately 10 degrees greater than that of GWALP23. The presence of R14 furthermore induces bilayer thinning and peptide displacement to "lift" the charged guanidinium toward the bilayer surface. By contrast, GWALP23-R12 exhibits multiple states that are in slow exchange on the NMR time scale, with CG-MD simulations indicating two distinct positions with different screw rotation angles in the membrane, along with an increased tendency to exit the lipid bilayer.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA.
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Vostrikov
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Hall
authors.forename: Denise V
authors.initials: DV
authors.lastname: Greathouse
authors.forename: Roger E
authors.initials: RE
authors.lastname: Koeppe
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001120:Arginine; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012399:Rotation
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides; D001120:Arginine