1ho9
BEST 20 NMR CONFORMERS OF D130I MUTANT T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA 2A ADRENERGIC RECEPTOR
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OverviewOverview
A major, unresolved question in signal transduction by G protein coupled, receptors (GPCRs) is to understand how, at atomic resolution, a GPCR, activates a G protein. A step toward answering this question was made with, the determination of the high-resolution structure of rhodopsin; we now, know the intramolecular interactions that characterize the resting, conformation of a GPCR. To what degree does this structure represent a, structural paradigm for other GPCRs, especially at the cytoplasmic surface, where GPCR-G protein interaction occurs and where the sequence homology is, low among GPCRs? To address this question, we performed NMR studies on, approximately 35-residue-long peptides including the critical second, intracellular loop (i2) of the alpha 2A adrenergic receptor (AR) and of, rhodopsin. To stabilize the secondary structure of the peptide termini, 4-12 residues from the adjacent transmembrane helices were included and, structures determined in dodecylphosphocholine micelles. We also, characterized the effects on an alpha 2A AR peptide of a D130I mutation in, the conserved DRY motif. Our results show that in contrast to the L-shaped, loop in the i2 of rhodopsin, the i2 of the alpha 2A AR is predominantly, helical, supporting the hypothesis that there is structural diversity, within GPCR intracellular loops. The D130I mutation subtly modulates the, helical structure. The spacing of nonpolar residues in i2 with helical, periodicity is a predictor of helical versus loop structure. These data, should lead to more accurate models of the intracellular surface of GPCRs, and of receptor-mediated G protein activation.
About this StructureAbout this Structure
1HO9 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix., Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR, Biochemistry. 2002 Mar 19;41(11):3596-604. PMID:11888275
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