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PDBsum entry 3ije
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Protein binding
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PDB id
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3ije
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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 complete integrin alphavbeta3 ectodomain plus an alpha/beta transmembrane fragment.
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Authors
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J.P.Xiong,
B.Mahalingham,
J.L.Alonso,
L.A.Borrelli,
X.Rui,
S.Anand,
B.T.Hyman,
T.Rysiok,
D.Müller-Pompalla,
S.L.Goodman,
M.A.Arnaout.
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Ref.
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J Cell Biol, 2009,
186,
589-600.
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PubMed id
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Abstract
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We determined the crystal structure of 1TM-alphaVbeta3, which represents the
complete unconstrained ectodomain plus short C-terminal transmembrane stretches
of the alphaV and beta3 subunits. 1TM-alphaVbeta3 is more compact and less
active in solution when compared with DeltaTM-alphaVbeta3, which lacks the short
C-terminal stretches. The structure reveals a bent conformation and defines the
alpha-beta interface between IE2 (EGF-like 2) and the thigh domains. Modifying
this interface by site-directed mutagenesis leads to robust integrin activation.
Fluorescent lifetime imaging microscopy of inactive full-length alphaVbeta3 on
live cells yields a donor-membrane acceptor distance, which is consistent with
the bent conformation and does not change in the activated integrin. These data
are the first direct demonstration of conformational coupling of the integrin
leg and head domains, identify the IE2-thigh interface as a critical steric
barrier in integrin activation, and suggest that inside-out activation in intact
cells may involve conformational changes other than the postulated switch to a
genu-linear state.
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