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PDBsum entry 4g1m
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Protein binding
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PDB id
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4g1m
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References listed in PDB file
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Key reference
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Title
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α(V)β(3) integrin crystal structures and their functional implications.
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Authors
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X.Dong,
L.Z.Mi,
J.Zhu,
W.Wang,
P.Hu,
B.H.Luo,
T.A.Springer.
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Ref.
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Biochemistry, 2012,
51,
8814-8828.
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PubMed id
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Abstract
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Many questions about the significance of structural features of integrin
α(V)β(3) with respect to its mechanism of activation remain. We have
determined and re-refined crystal structures of the α(V)β(3) ectodomain linked
to C-terminal coiled coils (α(V)β(3)-AB) and four transmembrane (TM) residues
in each subunit (α(V)β(3)-1TM), respectively. The α(V) and β(3) subunits
with four and eight extracellular domains, respectively, are bent at knees
between the integrin headpiece and lower legs, and the headpiece has the closed,
low-affinity conformation. The structures differ in the occupancy of three
metal-binding sites in the βI domain. Occupancy appears to be related to the pH
of crystallization, rather than to the physiologic regulation of ligand binding
at the central, metal ion-dependent adhesion site. No electron density was
observed for TM residues and much of the α(V) linker. α(V)β(3)-AB and
α(V)β(3)-1TM demonstrate flexibility in the linker between their extracellular
and TM domains, rather than the previously proposed rigid linkage. A previously
postulated interface between the α(V) and β(3) subunits at their knees was
also not supported, because it lacks high-quality density, required rebuilding
in α(V)β(3)-1TM, and differed markedly between α(V)β(3)-1TM and
α(V)β(3)-AB. Together with the variation in domain-domain orientation within
their bent ectodomains between α(V)β(3)-AB and α(V)β(3)-1TM, these findings
are compatible with the requirement for large structural changes, such as
extension at the knees and headpiece opening, in conveying activation signals
between the extracellular ligand-binding site and the cytoplasm.
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