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4bk4

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Revision as of 07:44, 3 April 2019

crystal structure of the human EphA4 ectodomain

Structural highlights

4bk4 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Receptor protein-tyrosine kinase, with EC number 2.7.10.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EPHA4_HUMAN] Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. Beside its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.^[1]

Publication Abstract from PubMed

Functional outcomes of ephrin binding to Eph receptors (Ephs) range from cell repulsion to adhesion. Here we used cell collapse and stripe assays, showing contrasting effects of human ephrinA5 binding to EphA2 and EphA4. Despite equivalent ligand binding affinities, EphA4 triggered greater cell collapse, whereas EphA2-expressing cells adhered better to ephrinA5-coated surfaces. Chimeric receptors showed that the ectodomain is a major determinant of cell response. We report crystal structures of EphA4 ectodomain alone and in complexes with ephrinB3 and ephrinA5. These revealed closed clusters with a dimeric or circular arrangement in the crystal lattice, contrasting with extended arrays previously observed for EphA2 ectodomain. Localization microscopy showed that ligand-stimulated EphA4 induces smaller clusters than does EphA2. Mutant Ephs link these characteristics to interactions observed in the crystal lattices, suggesting a mechanism by which distinctive ectodomain surfaces determine clustering, and thereby signaling, properties.

Structurally encoded intraclass differences in EphA clusters drive distinct cell responses.,Seiradake E, Schaupp A, Del Toro Ruiz D, Kaufmann R, Mitakidis N, Harlos K, Aricescu AR, Klein R, Jones EY Nat Struct Mol Biol. 2013 Jun 30. doi: 10.1038/nsmb.2617. PMID:23812375^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fu WY, Chen Y, Sahin M, Zhao XS, Shi L, Bikoff JB, Lai KO, Yung WH, Fu AK, Greenberg ME, Ip NY. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat Neurosci. 2007 Jan;10(1):67-76. Epub 2006 Dec 3. PMID:17143272 doi:10.1038/nn1811
↑ Seiradake E, Schaupp A, Del Toro Ruiz D, Kaufmann R, Mitakidis N, Harlos K, Aricescu AR, Klein R, Jones EY. Structurally encoded intraclass differences in EphA clusters drive distinct cell responses. Nat Struct Mol Biol. 2013 Jun 30. doi: 10.1038/nsmb.2617. PMID:23812375 doi:10.1038/nsmb.2617

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bk4"

@@ Line 1: / Line 1: @@
 ==crystal structure of the human EphA4 ectodomain==
-<StructureSection load='4bk4' size='340' side='right' caption='[[4bk4]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
+<StructureSection load='4bk4' size='340' side='right'caption='[[4bk4]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4bk4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BK4 FirstGlance]. <br>
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 4bk4" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ephrin receptor|Ephrin receptor]]
 == References ==
 <references/>
@@ Line 23: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Receptor protein-tyrosine kinase]]
 [[Category: Aricescu, A R]]

4bk4

From Proteopedia

Revision as of 07:44, 3 April 2019

crystal structure of the human EphA4 ectodomain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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