4h39

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of JNK3 in Complex with JIP1 Peptide

Structural highlights

4h39 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.992Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MK10_HUMAN Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:606369. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.

Function

MK10_HUMAN Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.^[1]

Publication Abstract from PubMed

c-Jun N-terminal (JNK) family kinases have a common peptide-docking site used by upstream activating kinases, substrates, scaffold proteins, and phosphatases, where the ensemble of bound proteins determines signaling output. Although there are many JNK structures, little is known about mechanisms of allosteric regulation between the catalytic and peptide-binding sites, and the activation loop, whose phosphorylation is required for catalytic activity. Here, we compare three structures of unliganded JNK3 bound to different peptides. These were compared as a class to structures that differ in binding of peptide, small molecule ligand, or conformation of the kinase activation loop. Peptide binding induced an inhibitory interlobe conformer that was reversed by alterations in the activation loop. Structure class analysis revealed the subtle structural mechanisms for allosteric signaling between the peptide-binding site and activation loop. Biochemical data from isothermal calorimetry, fluorescence energy transfer, and enzyme inhibition demonstrated affinity differences among the three peptides that were consistent with structural observations.

Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases.,Laughlin JD, Nwachukwu JC, Figuera-Losada M, Cherry L, Nettles KW, Lograsso PV Structure. 2012 Nov 6. pii: S0969-2126(12)00374-7. doi:, 10.1016/j.str.2012.09.021. PMID:23142346^[2]

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

References

↑ Neidhart S, Antonsson B, Gillieron C, Vilbois F, Grenningloh G, Arkinstall S. c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10. FEBS Lett. 2001 Nov 16;508(2):259-64. PMID:11718727
↑ Laughlin JD, Nwachukwu JC, Figuera-Losada M, Cherry L, Nettles KW, Lograsso PV. Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases. Structure. 2012 Nov 6. pii: S0969-2126(12)00374-7. doi:, 10.1016/j.str.2012.09.021. PMID:23142346 doi:http://dx.doi.org/10.1016/j.str.2012.09.021

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4h39"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4h39]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H39 FirstGlance]. <br>
-</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=4h39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h39 OCA], [https://pdbe.org/4h39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h39 RCSB], [https://www.ebi.ac.uk/pdbsum/4h39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h39 ProSAT]</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]] 1.992&#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=4h39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h39 OCA], [https://pdbe.org/4h39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h39 RCSB], [https://www.ebi.ac.uk/pdbsum/4h39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h39 ProSAT]</span></td></tr>
 </table>
 == Disease ==

4h39

From Proteopedia

Current revision

Crystal Structure of JNK3 in Complex with JIP1 Peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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