Three dimensional structure of the seventh transmembrane helical domainof the G-protein receptor, rhodopsin

[摘要] Purpose: The three dimensional structure of a peptide comprising thesequence of the seventh transmembrane segment of the G-protein coupledreceptor, rhodopsin, was determined in solution.Methods: The sequence of the seventh transmembrane segment ofrhodopsin, which contains the NPxxY sequence that is highly conservedamong G-protein coupled receptors and lys296 that forms the Schiff basewith the retinal, was synthesized by solid phase peptide synthesis. Thethree dimensional structure was determined in solution byhigh-resolution nuclear magnetic resonance (NMR).Results: The structure revealed a helix-break-helix motif for thissequence. Two families of structures were observed which differed inthe angle between the two helical segments. The sequence of thistransmembrane segment overlapped significantly the sequence of apeptide from the carboxyl terminal of rhodopsin, the structure of whichwas solved previously. The redundant sequence formed a helix in bothpeptides. It was therefore possible to superimpose the redundantsequence of both peptides and construct a structure for rhodopsinencompassing residues 291-348.Conclusions: This structure reveals locations of the lys296 and theacylation sites of rhodopsin that are consistent with the knownbiochemistry of this receptor. This segmentation approach to membraneprotein structure provides important structural information in theabsence of an X-ray crystal structure of rhodopsin. The approach isexpected to be useful for other G-protein coupled receptors.

[学科分类] 生物化学/生物物理