Solution structure of the cytoplasmic linker between domain III-S6 and domain IV-S1 (III-IV linker) of the rat brain sodium channel in SDS micelles

Citation
K. Miyamoto et al., Solution structure of the cytoplasmic linker between domain III-S6 and domain IV-S1 (III-IV linker) of the rat brain sodium channel in SDS micelles, BIOPOLYMERS, 59(5), 2001, pp. 380-393
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOPOLYMERS
ISSN journal
0006-3525 → ACNP
Volume
59
Issue
5
Year of publication
2001
Pages
380 - 393
Database
ISI
SICI code
0006-3525(20011015)59:5<380:SSOTCL>2.0.ZU;2-G
Abstract
The solution structure of the 36-mer peptide MP-5A in SDS micelles was inve stigated by CD and H-1-NMR spectroscopies. The MP-5A was dissected from the cytoplasmic linker (K1482-A1517) connecting domain III-segment 6 (IIIS6) a nd domain IV-segment 1 (IVS1; III-IV linker) of the rat brain type ITA sodi um channel. The molecular energy calculations including nuclear Overhauser effect and dihedral angle restraints gave a well-converged set of the struc tures of MP-5A for the region between I1488 and S1506. It was found that a large hydrophobic cluster is formed by I1488-F1489-M1490 (IFM motif), Y1497 -Y1498, and M1501, which may be related to the fast inactivation process of the sodium channel. The solvent-accessible surface area of the IFM motif ( 195 Angstrom (2)), which is known to work essentially as an inactivation ga te particle to occlude the ion permeation pore, gave the free energy (Delta G) of stabilization of -3.9 kcal mol(-1) as a result of the hydrophobic int eractions with its receptor. This value agreed well with the free energy of binding (inactivation) of -4.1 kcal mol(-1) calculated for the equilibrium between the open and the inactivated states of the sodium channels. It is concluded that the fast inactivation of the sodium channel is achieved by t he environmental polarity-dependent conformational switching at the IFM mot if in response to the voltage-dependent activation and the movement of the S4 segments of the sodium channel. (C) 2001 John Wiley & Sons, Inc.