1shw: Difference between revisions

Revision as of 16:01, 21 February 2008

EphB2 / EphrinA5 Complex Structure

OverviewOverview

The interactions between Eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding. The EphA receptors are generally thought to become activated by ephrin-A ligands, whereas the EphB receptors interact with ephrin-B ligands. Here we show that two of the most widely studied of these molecules, EphB2 and ephrin-A5, which have never been described to interact with each other, do in fact bind one another with high affinity. Exposure of EphB2-expressing cells to ephrin-A5 leads to receptor clustering, autophosphorylation and initiation of downstream signaling. Ephrin-A5 induces EphB2-mediated growth cone collapse and neurite retraction in a model system. We further show, using X-ray crystallography, that the ephrin-A5-EphB2 complex is a heterodimer and is architecturally distinct from the tetrameric EphB2-ephrin-B2 structure. The structural data reveal the molecular basis for EphB2-ephrin-A5 signaling and provide a framework for understanding the complexities of functional interactions and crosstalk between A- and B-subclass Eph receptors and ephrins.

About this StructureAbout this Structure

1SHW is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling., Himanen JP, Chumley MJ, Lackmann M, Li C, Barton WA, Jeffrey PD, Vearing C, Geleick D, Feldheim DA, Boyd AW, Henkemeyer M, Nikolov DB, Nat Neurosci. 2004 May;7(5):501-9. Epub 2004 Apr 25. PMID:15107857

Page seeded by OCA on Thu Feb 21 15:01:43 2008

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OCA

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-[[Image:1shw.gif|left|200px]]<br /><applet load="1shw" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1shw.gif|left|200px]]<br /><applet load="1shw" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1shw, resolution 2.2&Aring;" />
 '''EphB2 / EphrinA5 Complex Structure'''<br />
 ==Overview==
-The interactions between Eph receptor tyrosine kinases and their ephrin, ligands regulate cell migration and axon pathfinding. The EphA receptors, are generally thought to become activated by ephrin-A ligands, whereas the, EphB receptors interact with ephrin-B ligands. Here we show that two of, the most widely studied of these molecules, EphB2 and ephrin-A5, which, have never been described to interact with each other, do in fact bind one, another with high affinity. Exposure of EphB2-expressing cells to, ephrin-A5 leads to receptor clustering, autophosphorylation and initiation, of downstream signaling. Ephrin-A5 induces EphB2-mediated growth cone, collapse and neurite retraction in a model system. We further show, using, X-ray crystallography, that the ephrin-A5-EphB2 complex is a heterodimer, and is architecturally distinct from the tetrameric EphB2-ephrin-B2, structure. The structural data reveal the molecular basis for, EphB2-ephrin-A5 signaling and provide a framework for understanding the, complexities of functional interactions and crosstalk between A- and, B-subclass Eph receptors and ephrins.
+The interactions between Eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding. The EphA receptors are generally thought to become activated by ephrin-A ligands, whereas the EphB receptors interact with ephrin-B ligands. Here we show that two of the most widely studied of these molecules, EphB2 and ephrin-A5, which have never been described to interact with each other, do in fact bind one another with high affinity. Exposure of EphB2-expressing cells to ephrin-A5 leads to receptor clustering, autophosphorylation and initiation of downstream signaling. Ephrin-A5 induces EphB2-mediated growth cone collapse and neurite retraction in a model system. We further show, using X-ray crystallography, that the ephrin-A5-EphB2 complex is a heterodimer and is architecturally distinct from the tetrameric EphB2-ephrin-B2 structure. The structural data reveal the molecular basis for EphB2-ephrin-A5 signaling and provide a framework for understanding the complexities of functional interactions and crosstalk between A- and B-subclass Eph receptors and ephrins.
 ==About this Structure==
-SHW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SHW OCA].
+SHW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SHW OCA].
 ==Reference==
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 [[Category: Mus musculus]]
 [[Category: Protein complex]]
-[[Category: Barton, W.A.]]
+[[Category: Barton, W A.]]
-[[Category: Boyd, A.W.]]
+[[Category: Boyd, A W.]]
-[[Category: Chumley, M.J.]]
+[[Category: Chumley, M J.]]
-[[Category: Feldheim, D.A.]]
+[[Category: Feldheim, D A.]]
 [[Category: Geleick, D.]]
-[[Category: Himanen, J.P.]]
+[[Category: Himanen, J P.]]
-[[Category: Jeffrey, P.D.]]
+[[Category: Jeffrey, P D.]]
 [[Category: Lackmann, M.]]
 [[Category: Li, C.]]
@@ Line 27: / Line 27: @@
 [[Category: receptor tyrosine kinase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:23:46 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:43 2008''