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PDBsum entry 1jpa
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Contents |
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* Residue conservation analysis
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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 basis for autoinhibition of the ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region.
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Authors
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L.E.Wybenga-Groot,
B.Baskin,
S.H.Ong,
J.Tong,
T.Pawson,
F.Sicheri.
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Ref.
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Cell, 2001,
106,
745-757.
[DOI no: ]
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PubMed id
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Abstract
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The Eph receptor tyrosine kinase family is regulated by autophosphorylation
within the juxtamembrane region and the kinase activation segment. We have
solved the X-ray crystal structure to 1.9 A resolution of an autoinhibited,
unphosphorylated form of EphB2 comprised of the juxtamembrane region and the
kinase domain. The structure, supported by mutagenesis data, reveals that the
juxtamembrane segment adopts a helical conformation that distorts the small lobe
of the kinase domain, and blocks the activation segment from attaining an
activated conformation. Phosphorylation of conserved juxtamembrane tyrosines
would relieve this autoinhibition by disturbing the association of the
juxtamembrane segment with the kinase domain, while liberating phosphotyrosine
sites for binding SH2 domains of target proteins. We propose that the
autoinhibitory mechanism employed by EphB2 is a more general device through
which receptor tyrosine kinases are controlled.
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Figure 4.
Figure 4. Electrostatic Surface Representation of EphB2Blue
and red regions indicate positive and negative potential,
respectively (10 to −10 k[B]T). Phosphoregulatory residues
Tyr/Phe604 and Tyr/Phe610 are colored light blue. The molecular
surface of EphB2 is oriented as in Figure 2a and was generated
using GRASP (Nicholls et al., 1991)
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Figure 6.
Figure 6. Schematic Diagram Highlighting Difference between
the Autoinhibited and Active States of the Eph Receptor Family
of Tyrosine KinasesThe active configuration is based on the
crystal structure of active IRK (Protein Data Bank ID 1ir3).
Dashed lines indicate regions of activation segment disorder.
The numbering scheme corresponds to murine EphB2
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2001,
106,
745-757)
copyright 2001.
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