Molecular modeling and dynamics of the sodium channel inactivation gate.
The intracellular linker L(III-IV) of voltage-gated sodium channels is known to be involved in their mechanism of inactivation. Its primary sequence is well conserved in sodium channels from different tissues and species. However, the role of charged residues in this region, first thought to play an important role in inactivation, has not been well identified, whereas the IFM triad (I1488-M1490) has been characterized as the crucial element for inactivation. In this work, we constructed theoretical models and performed molecular dynamics simulations, exploring the role of L(III-IV)-charged residues in the presence of a polar/nonpolar planar interface represented by a dielectric discontinuity. From structural predictions, two alpha-helical segments are proposed. Moreover, from dynamics simulations, a time-conserved motif is detected and shown to play a relevant role in guiding the inactivation particle toward its receptor site.
Sirota
Fernanda L
FL
Instituto de Biofísica Carlos Chagas Filho UFRJ - Universidade Federal do Rio de Janeiro, Brazil.
Pascutti
Pedro G
PG
Anteneodo
Celia
C
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry*; D013696:Temperature
D000596:Amino Acids; D015222:Sodium Channels