signalling across membranes

Cornelius Krasel krasel at wpxx02.toxi.uni-wuerzburg.de
Wed Jun 27 12:56:05 EST 2001

jens <lohrmann at sun2.ruf.uni-freiburg.de> wrote:
> How do the 7 transmembrane (G-protein coupled) receptors signal the
> information across the membrane? is there anything known which is more
> specific than the rather fuzzy "conformational change"...?

With the crystal structure of rhodopsin there have been new ideas
on how a G-protein-coupled receptors changes its conformation to
mediate signaling, but there is no definitive answer yet. It seems
quite clear from studies using EPR spectroscopy and Zn crosslinking
that a movement of helix 3 and helix 6 is involved; mutagenesis studies
suggest that the DRY motif in the second intracellular loop also plays
a crucial part in G-protein activation. It has been hypothesized that
the arginine in this motif may be the final trigger for inducing the
conformational change in the G-protein, but I don't know whether this
is still the case.

Unfortunately, many of the suggestions how G-protein-coupled receptors
are activated do not address recent evidence that these receptors may
be multimeric proteins. There is some evidence that dimerization of
the beta2-adrenergic receptor may occur upon agonist binding, but these
results cannot be generalized.


/* Cornelius Krasel, U Wuerzburg, Dept. of Pharmacology, Versbacher Str. 9 */
/* D-97078 Wuerzburg, Germany   email: krasel at wpxx02.toxi.uni-wuerzburg.de */
/* "Science is the game we play with God to find out what His rules are."  */

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