1nuk

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF THE LIGAND-BINDING DOMAIN OF THE EPHB2 RECEPTOR TYROSINE KINASE

Structural highlights

1nuk is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EPHB2_MOUSE Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Eph receptors, which bind a group of cell-membrane-anchored ligands known as ephrins, represent the largest subfamily of receptor tyrosine kinases (RTKs). They are predominantly expressed in the developing and adult nervous system and are important in contact-mediated axon guidance, axon fasciculation and cell migration. Eph receptors are unique among other RTKs in that they fall into two subclasses with distinct ligand specificities, and in that they can themselves function as ligands to activate bidirectional cell-cell signalling. We report here the crystal structure at 2.9 A resolution of the amino-terminal ligand-binding domain of the EphB2 receptor (also known as Nuk). The domain folds into a compact jellyroll beta-sandwich composed of 11 antiparallel beta-strands. Using structure-based mutagenesis, we have identified an extended loop that is important for ligand binding and class specificity. This loop, which is conserved within but not between Eph RTK subclasses, packs against the concave beta-sandwich surface near positions at which missense mutations cause signalling defects, localizing the ligand-binding region on the surface of the receptor.

Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2.,Himanen JP, Henkemeyer M, Nikolov DB Nature. 1998 Dec 3;396(6710):486-91. PMID:9853759^[8]

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

References

↑ Henkemeyer M, Orioli D, Henderson JT, Saxton TM, Roder J, Pawson T, Klein R. Nuk controls pathfinding of commissural axons in the mammalian central nervous system. Cell. 1996 Jul 12;86(1):35-46. PMID:8689685
↑ Orioli D, Henkemeyer M, Lemke G, Klein R, Pawson T. Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation. EMBO J. 1996 Nov 15;15(22):6035-49. PMID:8947026
↑ Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999 Feb 1;13(3):295-306. PMID:9990854
↑ Cowan CA, Yokoyama N, Bianchi LM, Henkemeyer M, Fritzsch B. EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron. 2000 May;26(2):417-30. PMID:10839360
↑ Henkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM. Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol. 2003 Dec 22;163(6):1313-26. PMID:14691139 doi:http://dx.doi.org/10.1083/jcb.200306033
↑ Dravis C, Yokoyama N, Chumley MJ, Cowan CA, Silvany RE, Shay J, Baker LA, Henkemeyer M. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol. 2004 Jul 15;271(2):272-90. PMID:15223334 doi:http://dx.doi.org/10.1016/j.ydbio.2004.03.027
↑ Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, Mardinly AR, Hu L, Greer PL, Bikoff JB, Ho HY, Soskis MJ, Sahin M, Greenberg ME. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell. 2010 Oct 29;143(3):442-55. doi: 10.1016/j.cell.2010.09.038. PMID:21029865 doi:http://dx.doi.org/10.1016/j.cell.2010.09.038
↑ Himanen JP, Henkemeyer M, Nikolov DB. Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2. Nature. 1998 Dec 3;396(6710):486-91. PMID:9853759 doi:10.1038/24904

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1nuk"

Categories: Large Structures | Mus musculus | Henkemeyer M | Himanen J-P | Nikolov DB

@@ Line 3: / Line 3: @@
 <StructureSection load='1nuk' size='340' side='right'caption='[[1nuk]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1nuk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NUK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1nuk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NUK FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nuk OCA], [https://pdbe.org/1nuk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nuk RCSB], [https://www.ebi.ac.uk/pdbsum/1nuk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nuk ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/EPHB2_MOUSE EPHB2_MOUSE]] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.<ref>PMID:8689685</ref> <ref>PMID:8947026</ref> <ref>PMID:9990854</ref> <ref>PMID:10839360</ref> <ref>PMID:14691139</ref> <ref>PMID:15223334</ref> <ref>PMID:21029865</ref>
+[https://www.uniprot.org/uniprot/EPHB2_MOUSE EPHB2_MOUSE] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.<ref>PMID:8689685</ref> <ref>PMID:8947026</ref> <ref>PMID:9990854</ref> <ref>PMID:10839360</ref> <ref>PMID:14691139</ref> <ref>PMID:15223334</ref> <ref>PMID:21029865</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 14: / Line 14: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nu/1nuk_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Transferase]]
+[[Category: Henkemeyer M]]
-[[Category: Henkemeyer, M]]
+[[Category: Himanen J-P]]
-[[Category: Himanen, J P]]
+[[Category: Nikolov DB]]
-[[Category: Nikolov, D B]]
-[[Category: Eph receptor tyrosine kinase]]

1nuk

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF THE LIGAND-BINDING DOMAIN OF THE EPHB2 RECEPTOR TYROSINE KINASE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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