Solution structures of the cytoplasmic linkers between segments S-4 and S-5 (S-4-S-5) in domains III and IV of human brain sodium channels in SDS micelles

Citation
K. Miyamoto et al., Solution structures of the cytoplasmic linkers between segments S-4 and S-5 (S-4-S-5) in domains III and IV of human brain sodium channels in SDS micelles, J PEPT RES, 58(3), 2001, pp. 193-203
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF PEPTIDE RESEARCH
ISSN journal
1397-002X → ACNP
Volume
58
Issue
3
Year of publication
2001
Pages
193 - 203
Database
ISI
SICI code
1397-002X(200109)58:3<193:SSOTCL>2.0.ZU;2-6
Abstract
The two cytoplasmic linkers connecting segment S4 and segment S5 (S4-S5 lin ker) of both domain III (III/S4-S5) and IV (IV/S4-S5) of the sodium channel a-subunit are considered to work as a hydrophobic receptor for the inactiv ation particle because of the three hydrophobic amino acids of Ile-Phe-Met (IFM motif) in the III-IV linker of the sodium channel chi -subunit. To dat e, the solution structures of the peptides related to III/S4-S5 (MP-D3: A13 25-M1338) and IV/S4-S5 (MP-D4: T1648-L1666) of human brain sodium channels have been investigated using CD and H-1 NMR spectroscopies. SIDS micelles w ere employed as a solvent. The micelles mimic either biological membranes o r the interior of a protein and can be a relevant environment at the inacti vated state of the channels. It was found that the secondary structures of both MP-D3 and MP-D4 assume chi -helical conformations around the N-termina l 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 i s considered to interact with F1489 of the IFM motif, was found to be locat ed within the chi -helix. Residues F1651, M1654, M1655, L1657 and A1669 in MP-D4, which also play an important role in inactivation, formed a hydropho bic cluster on one side of the helix. This cluster was concluded to Dates: interact with the hydrophobic cluster due to the III-IV linker before the i nactivation gate closes.