Dissecting intersubunit contacts in cyclic nucleotide-gated ion channels

Neuron. 2002 Feb 28;33(5):703-13. doi: 10.1016/s0896-6273(02)00599-8.

Abstract

In cyclic nucleotide-gated (CNG) ion channels, binding of cGMP or cAMP drives a conformational change that leads to opening of an ion-conducting pore. One region implicated in the coupling of ligand binding to opening of the pore is the C linker region. Here, we used crosslinking of endogenous cysteines to study interregion proximity. We demonstrate that an individual amino acid--C481--in the C linker region of each of two neighboring subunits can form a disulfide bond. Further, using tandem dimers, we show that a disulfide bond between C35 in the N-terminal region and C481 in the C linker region can form either within a subunit or between subunits. From our data on proximity between individual amino acids and previous studies, a picture emerges of the C linker as a potential dimerization interface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cyclic GMP / metabolism*
  • Cysteine / chemistry
  • Cysteine / metabolism*
  • Dimerization
  • Disulfides / chemistry
  • Dose-Response Relationship, Drug
  • Ion Channel Gating
  • Ion Channels / chemistry
  • Ion Channels / metabolism*
  • Models, Biological
  • Mutagenesis, Site-Directed
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Phenanthrolines / metabolism
  • Protein Binding
  • Protein Conformation*
  • Protein Subunits
  • Xenopus laevis / physiology

Substances

  • Disulfides
  • Ion Channels
  • Phenanthrolines
  • Protein Subunits
  • Cyclic GMP
  • Cysteine