Premium
Bundles of amphipathic transmembrane α‐helices as a structural motif for ion‐conducting channel proteins: Studies on sodium channels and acetylcholine receptors
Author(s) -
Oiki Shigetoshi,
Madison Vincent,
Montal Mauricio
Publication year - 1990
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340080305
Subject(s) - chemistry , ion channel , dihedral angle , helix bundle , transmembrane protein , crystallography , lipid bilayer , biophysics , ionic bonding , helix (gastropod) , amphiphile , transmembrane domain , supramolecular chemistry , nicotinic acetylcholine receptor , acetylcholine receptor , structural motif , bilayer , protein structure , ion , membrane , hydrogen bond , molecule , receptor , crystal structure , biochemistry , organic chemistry , biology , ecology , snail , copolymer , polymer
Channel proteins are transmembrane symmetric (or pseudosymmetric) oligomers organized around a central ionic pore. We present here a molecular model of the pore forming structures of two channel proteins with different primary structures and oligomeric size: the voltage‐sensitive sodium channel and the nicotinic cholinergic receptor. We report low‐energy arrangements of α‐helical bundles calculated by semiempiricial potential energy functions and optimization routines and further refined using molecular dynamics. The ion‐conducting pore is considered to be a symmetric or pseudosymmetric homooligomer of 3–5 amphipathic α‐helices arranged such that the polar residues line a central hydrophilic pathway and the apolar residues face the hydrophobic bilayer interior. The channel lining exposes either charged (Asp, Glu, Arg, Lys) or polar‐neutral (Ser, Thr) residues. A bundle of four parallel helices constrained to C 4 symmetry, the helix axis aligned with the symmetry axis, and the helices constrained to idealized dihedral angles, produces a structure with a pore of the size inferred for the sodium channel protein (area ∼ 16 Å 2 ). Similarly, a pentameric array optimized with constraints to maintain C 5 symmetry and backbone torsions characteristic of α‐helices adopts a structure that appears well suited to form the lining of the nicotinic cholinergic receptor (pore area ∼ 46 Å 2 ). Thus, bundles of amphipathic α‐helices satisfy the structural, energetic, and dynamic requirements to be the molecular structural motif underlying the function of ionic channels.