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PDBsum entry 3mbw
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Transferase/signaling protein
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PDB id
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3mbw
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References listed in PDB file
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Key reference
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Title
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Architecture of eph receptor clusters.
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Authors
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J.P.Himanen,
L.Yermekbayeva,
P.W.Janes,
J.R.Walker,
K.Xu,
L.Atapattu,
K.R.Rajashankar,
A.Mensinga,
M.Lackmann,
D.B.Nikolov,
S.Dhe-Paganon.
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Ref.
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Proc Natl Acad Sci U S A, 2010,
107,
10860-10865.
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PubMed id
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Abstract
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Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation
during normal and oncogenic development. Signaling of Ephs is initiated in a
multistep process leading to the assembly of higher-order signaling clusters
that set off bidirectional signaling in interacting cells. However, the
structural and mechanistic details of this assembly remained undefined. Here we
present high-resolution structures of the complete EphA2 ectodomain and
complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The
structures reveal an elongated architecture with novel Eph/Eph interactions,
both within and outside of the Eph ligand-binding domain, that suggest the
molecular mechanism underlying Eph/ephrin clustering. Structure-function
analysis, by using site-directed mutagenesis and cell-based signaling assays,
confirms the importance of the identified oligomerization interfaces for Eph
clustering.
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