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PDBsum entry 4um9
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Immune system
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PDB id
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4um9
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Contents |
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594 a.a.
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448 a.a.
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11 a.a.
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13 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 determinants of integrin β-Subunit specificity for latent tgf-β.
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Authors
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X.Dong,
N.E.Hudson,
C.Lu,
T.A.Springer.
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Ref.
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Nat Struct Biol, 2014,
21,
1091-1096.
[DOI no: ]
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PubMed id
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Abstract
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Eight integrin α-β heterodimers recognize ligands with an Arg-Gly-Asp (RGD)
motif. However, the structural mechanism by which integrins differentiate among
extracellular proteins with RGD motifs is not understood. Here, crystal
structures, mutations and peptide-affinity measurements show that αVβ6 binds
with high affinity to a RGDLXXL/I motif within the prodomains of TGF-β1 and
TGF-β3. The LXXL/I motif forms an amphipathic α-helix that binds in a
hydrophobic pocket in the β6 subunit. Elucidation of the basis for ligand
binding specificity by the integrin β subunit reveals contributions by three
different βI-domain loops, which we designate specificity-determining loops
(SDLs) 1, 2 and 3. Variation in a pair of single key residues in SDL1 and SDL3
correlates with the variation of the entire β subunit in integrin evolution,
thus suggesting a paradigmatic role in overall β-subunit function.
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