1hll: Difference between revisions

Revision as of 14:02, 21 February 2008

NMR STRUCTURE OF T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA-2A ADRENERGIC RECEPTOR

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

1HLL 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

Page seeded by OCA on Thu Feb 21 13:02:35 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1hll.gif|left|200px]]<br />
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 '''NMR STRUCTURE OF T3-I2, A 32 RESIDUE PEPTIDE FROM THE ALPHA-2A ADRENERGIC RECEPTOR'''<br />
 ==Overview==
-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.
+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 Structure==
-HLL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HLL OCA].
+HLL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HLL OCA].
 ==Reference==
 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11888275 11888275]
 [[Category: Single protein]]
-[[Category: Chung, D.A.]]
+[[Category: Chung, D A.]]
-[[Category: Neubig, R.R.]]
+[[Category: Neubig, R R.]]
-[[Category: Zuiderweg, E.R.P.]]
+[[Category: Zuiderweg, E R.P.]]
 [[Category: helix-linker-helix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:19:51 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:35 2008''