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PDBsum entry 6pwc
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Signaling protein
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PDB id
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6pwc
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Contents |
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323 a.a.
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350 a.a.
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194 a.a.
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183 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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A complex structure of arrestin-2 bound to a g protein-Coupled receptor.
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Authors
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W.Yin,
Z.Li,
M.Jin,
Y.L.Yin,
P.W.De waal,
K.Pal,
Y.Yin,
X.Gao,
Y.He,
J.Gao,
X.Wang,
Y.Zhang,
H.Zhou,
K.Melcher,
Y.Jiang,
Y.Cong,
X.Edward zhou,
X.Yu,
H.Eric xu.
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Ref.
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Cell Res, 2019,
29,
971-983.
[DOI no: ]
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PubMed id
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Abstract
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Arrestins comprise a family of signal regulators of G-protein-coupled receptors
(GPCRs), which include arrestins 1 to 4. While arrestins 1 and 4 are visual
arrestins dedicated to rhodopsin, arrestins 2 and 3 (Arr2 and Arr3) are
β-arrestins known to regulate many nonvisual GPCRs. The dynamic and promiscuous
coupling of Arr2 to nonvisual GPCRs has posed technical challenges to tackle the
basis of arrestin binding to GPCRs. Here we report the structure of Arr2 in
complex with neurotensin receptor 1 (NTSR1), which reveals an overall assembly
that is strikingly different from the visual arrestin-rhodopsin complex by a
90° rotation of Arr2 relative to the receptor. In this new configuration,
intracellular loop 3 (ICL3) and transmembrane helix 6 (TM6) of the receptor are
oriented toward the N-terminal domain of the arrestin, making it possible for
GPCRs that lack the C-terminal tail to couple Arr2 through their ICL3. Molecular
dynamics simulation and crosslinking data further support the assembly of the
Arr2‒NTSR1 complex. Sequence analysis and homology modeling suggest that the
Arr2‒NTSR1 complex structure may provide an alternative template for modeling
arrestin-GPCR interactions.
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