Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Trends Pharmacol Sci

Publication Date

11/2000

Volume

21

Pages

445 - 451

Keywords

ATP Binding Cassette Transporter, Sub-Family B, Amino Acid Sequence, Animals, Connexins, Humans, Ion Channels, Membrane Proteins, Molecular Sequence Data, Proline, Protein Conformation, Protein Structure, Secondary, Receptors, Cell Surface, Signal Transduction