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PDBsum entry 6pyh
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Signaling protein/hormone
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PDB id
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6pyh
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Contents |
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793 a.a.
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57 a.a.
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798 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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Structural basis of the activation of type 1 insulin-Like growth factor receptor.
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Authors
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J.Li,
E.Choi,
H.Yu,
X.C.Bai.
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Ref.
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Nat Commun, 2019,
10,
4567.
[DOI no: ]
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PubMed id
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Abstract
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Type 1 insulin-like growth factor receptor (IGF1R) is a receptor tyrosine kinase
that regulates cell growth and proliferation, and can be activated by IGF1,
IGF2, and insulin. Here, we report the cryo-EM structure of full-length
IGF1R-IGF1 complex in the active state. This structure reveals that only one
IGF1 molecule binds the Γ-shaped asymmetric IGF1R dimer. The IGF1-binding site
is formed by the L1 and CR domains of one IGF1R protomer and the α-CT and
FnIII-1 domains of the other. The liganded α-CT forms a rigid beam-like
structure with the unliganded α-CT, which hinders the conformational change of
the unliganded α-CT required for binding of a second IGF1 molecule. We further
identify an L1-FnIII-2 interaction that mediates the dimerization of
membrane-proximal domains of IGF1R. This interaction is required for optimal
receptor activation. Our study identifies a source of the negative cooperativity
in IGF1 binding to IGF1R and reveals the structural basis of IGF1R activation.
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