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PDBsum entry 2r4r
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Signaling protein
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PDB id
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2r4r
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Contents |
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216 a.a.
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214 a.a.
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217 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the human beta2 adrenergic g-Protein-Coupled receptor.
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Authors
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S.G.Rasmussen,
H.J.Choi,
D.M.Rosenbaum,
T.S.Kobilka,
F.S.Thian,
P.C.Edwards,
M.Burghammer,
V.R.Ratnala,
R.Sanishvili,
R.F.Fischetti,
G.F.Schertler,
W.I.Weis,
B.K.Kobilka.
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Ref.
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Nature, 2007,
450,
383-387.
[DOI no: ]
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PubMed id
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Abstract
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Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and
neurotransmitters has been hindered by their low natural abundance, inherent
structural flexibility, and instability in detergent solutions. Here we report a
structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a
lipid environment when bound to an inverse agonist and in complex with a Fab
that binds to the third intracellular loop. Diffraction data were obtained by
high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A
resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the
connecting loops are well resolved, whereas the extracellular regions of the
beta2AR are not seen. The beta2AR structure differs from rhodopsin in having
weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6,
involving the conserved E/DRY sequences. These differences may be responsible
for the relatively high basal activity and structural instability of the
beta2AR, and contribute to the challenges in obtaining diffraction-quality
crystals of non-rhodopsin GPCRs.
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Figure 3.
Figure 3: Comparison of beta- [2]AR
and rhodopsin structures. a, The 
[2]AR is superimposed with the homologous structure of
rhodopsin^6. Retinal is shown in purple and the electron density
in the putative ligand-binding site is shown as a green mesh.
Structures were aligned using all seven transmembrane segments.
The right panels represent cross-sections that are rotated
90° around the horizontal axis and viewed from the
extracellular face of the receptor. b, Comparison of the [2]AR
with structures of inactive rhodopsin and light-activated
rhodopsin around the conserved E/DRY sequence in TM3. A
dashed line shows the distance between the homologous arginine
in TM3 and glutamate in TM6. To facilitate comparison of the
E/DRY regions, the structures were aligned by superimposing TM3
only.
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Figure 4.
Figure 4: Side-chain interactions between Leu 272 and residues
in TM3, TM5 and intracellular loop 2. Packing interactions
are reflected in lower B-factors for these amino acids. The
average B value of residues 135, 141, 219, 222, 272 and 275 is
117 Å^2, compared to 157 Å^2 for the receptor as a
whole.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2007,
450,
383-387)
copyright 2007.
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