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PDBsum entry 3hpn
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References listed in PDB file
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Key reference
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Title
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Ligand recognition by a-Class eph receptors: crystal structures of the epha2 ligand-Binding domain and the epha2/ephrin-A1 complex.
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Authors
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J.P.Himanen,
Y.Goldgur,
H.Miao,
E.Myshkin,
H.Guo,
M.Buck,
M.Nguyen,
K.R.Rajashankar,
B.Wang,
D.B.Nikolov.
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Ref.
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Embo Rep, 2009,
10,
722-728.
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PubMed id
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Abstract
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Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B)
according to preferences for their ephrin ligands. All published structural
studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we
present the crystal structures of an A-class complex between EphA2 and ephrin-A1
and of unbound EphA2. Although these structures are similar overall to their
B-class counterparts, they reveal important differences that define subclass
specificity. The structures suggest that the A-class Eph receptor/ephrin
interactions involve smaller rearrangements in the interacting partners, better
described by a 'lock-and-key'-type binding mechanism, in contrast to the
'induced fit' mechanism defining the B-class molecules. This model is supported
by structure-based mutagenesis and by differential requirements for ligand
oligomerization by the two subclasses in cell-based Eph receptor activation
assays. Finally, the structure of the unligated receptor reveals a homodimer
assembly that might represent EphA2-specific homotypic cell adhesion
interactions.
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