THE TRANSMEMBRANE 7-ALPHA-BUNDLE OF RHODOPSIN - DISTANCE GEOMETRY CALCULATIONS WITH HYDROGEN-BONDING CONSTRAINTS

A 3D model of the transmembrane 7-alpha-bundle of rhodopsin-like G-pro tein-coupled receptors (GPCRs) was calculated using an iterative dista nce geometry refinement with an evolving system of hydrogen bonds, for med by intramembrane polar side chains in various proteins of the fami ly and collectively applied as distance constraints. The alpha-bundle structure thus obtained provides H bonding of nearly all buried polar side chains simultaneously in the 410 GPCRs considered. Forty evolutio narily conserved GPCR residues form a single continuous domain, with a n aliphatic ''core'' surrounded by six clusters of polar and aromatic side chains. The 7-alpha-bundle of a specific GPCR can be calculated u sing its own set of H bonds as distance constraints and the common ''a verage'' model to restrain positions of the helices. The bovine rhodop sin model thus determined is closely packed, but has a few small polar cavities, presumably filled by water, and has a binding pocket that i s complementary to 11-cis (6-s-cis, 12-s-trans, C=N anti)-retinal or t o all-trans-retinal, depending on conformations of the Lys(296) and Tr p(265) side chains. A suggested mechanism of rhodopsin photoactivation , triggered by the cis-trans isomerization of retinal, involves rotati ons of Glu(134), Tyr(223), Trp(265), Lys(296), and Tyr(306) side chain s and rearrangement of their H bonds. The model is in agreement with p ublished electron cryomicroscopy, mutagenesis, chemical modification, cross-linking, Fourier transform infrared spectroscopy. Raman spectros copy, electron paramagnetic resonance spectroscopy, NMR, and optical s pectroscopy data. The rhodopsin model and the published structure of b acteriorhodopsin have very similar retinal-binding pockets.