title: Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4-S5) in domains III and IV of human brain sodium channels in SDS micelles.
abstract: The two cytoplasmic linkers connecting segment S4 and segment S5 (S4-S5 linker) of both domain III (III/S4-S5) and IV (IV/S4-S5) of the sodium channel alpha-subunit are considered to work as a hydrophobic receptor for the inactivation particle because of the three hydrophobic amino acids of Ile-Phe-Met (IFM motif) in the III-IV linker of the sodium channel alpha-subunit. To date, the solution structures of the peptides related to III/S4-S5 (MP-D3: A1325-M1338) and IV/S4-S5 (MP-D4: T1648-L1666) of human brain sodium channels have been investigated using CD and (1)H NMR spectroscopies. SDS micelles were employed as a solvent. The micelles mimic either biological membranes or the interior of a protein and can be a relevant environment at the inactivated state of the channels. It was found that the secondary structures of both MP-D3 and MP-D4 assume alpha-helical conformations around the N-terminal half-side of the sequences, i.e. the residues between V1326 and L1331 in MP-D3 and between L1650 and S1656 in MP-D4. Residue A1329 in MP-D3, which is considered to interact with F1489 of the IFM motif, was found to be located within the alpha-helix. Residues F1651, M1654, M1655, L1657 and A1669 in MP-D4, which also play an important role in inactivation, formed a hydrophobic cluster on one side of the helix. This cluster was concluded to interact with the hydrophobic cluster due to the III-IV linker before the inactivation gate closes.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D020816:Amino Acid Motifs; D001923:Brain Chemistry; D002942:Circular Dichroism; D003593:Cytoplasm / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015222:Sodium Channels / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012996:Solutions / Q000737:chemistry
chemical_list: D008823:Micelles; D010446:Peptide Fragments; D015222:Sodium Channels; D012996:Solutions; D012967:Sodium Dodecyl Sulfate