Just an idea, but I would welcome criticism from this forum:
My interests include "7TM" receptors coupled to GTP-binding proteins.
Since "7TM" receptors are integral membrane proteins, they have proven
refractory to known approaches for crystallization and structural solution
(as I understand it).
Of course, the single exception to this is the electron diffraction approach
used by Henderson and colleagues for bacterial-rhodopsin. This structure
serves as a prototype for my field, but since it is not a G-protein-linked
receptor, this interpretation should be cautious. My limited knowledge
of 7TM protein models is that these are fundamentally derived from the
prediction that bacterial-rhodopsin is composed of a concentric ring of
seven alpha-helical membrane spanning domains.
But if one produces segments of a 7TM receptor protein, each containing a single
predicted membrane spanning region, what is the likelihood that these
segments could be crystallized, and solved individually? Has anyone
published a structure for any other membrane spanning protein that
includes the membrane spanning region in the crystal? Is this idea
totally bone-headed, or does anyone think it would have a chance for
The questions I would hope to answer from this experiment are: 1) Are these
transmembrane regions amphipathic alpha-helical or otherwise, and 2) What are the relationships between amino acid residues within each of these predicted
transmembrane spanning domains?
Answering these questions (correctly) might prove valuable in
developing appropriate models for the structures of these proteins.
Again, I would appreciate any comments. Thanks.
Dept of Pharmacology
Emory University School of Medicine