Hinges, swivels and switches: the role of prolines in signalling via transmembrane alpha-helices. Review uri icon

Overview

abstract

  • Extracellular signals are transduced across membranes via conformational changes in the transmembrane domains (TMs) of ion channels and G-protein-coupled receptors (GPCRs). Experimental and simulation studies indicate that such conformational switches in transmembrane (alpha-helices can be generated by proline-containing motifs that form molecular hinges. Computational approaches tested on model channel-forming peptides (e.g. alamethicin) reveal functional mechanisms in gap-junction proteins (such as connexin) and voltage-gated K+ channels. Similarly, functionally important roles for proline-based switches in TM6 and TM7 were identified in GPCRs. However, hinges in transmembrane helices are not confined to proline-containing sequence motifs, as evidenced by a non-proline hinge in the M2 helix of the nicotinic acetylcholine receptor. This helix lines the pore and plays a key role in the gating of this channel.

publication date

  • November 1, 2000

Research

keywords

  • Membrane Proteins
  • Proline
  • Signal Transduction

Identity

Scopus Document Identifier

  • 0034327611

PubMed ID

  • 11121576

Additional Document Info

volume

  • 21

issue

  • 11