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4yl6

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Revision as of 17:05, 22 March 2017

Crystal structure of truncated cerebral cavernous malformation 2 C-terminal adaptor domain in complex with an internal helix of mitogen-activated protein kinase kinase kinase 3

Structural highlights

4yl6 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4ykc, 4ykd
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CCM2_HUMAN] Hereditary cerebral cavernous malformation. The disease is caused by mutations affecting the gene represented in this entry.

Function

[CCM2_HUMAN] Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions (By similarity). May function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock (By similarity). [M3K3_HUMAN] Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Cerebral cavernous malformation 2 (CCM2) functions as an adaptor protein implicated in various biological processes. By interacting with the mitogen-activated protein kinase MEKK3, CCM2 either mediates the activation of MEKK3 signaling in response to osmotic stress or negatively regulates MEKK3 signaling, which is important for normal cardiovascular development. However, the molecular basis governing CCM2-MEKK3 interaction is largely unknown. Here we report the crystal structure of the CCM2 C-terminal part (CCM2ct) containing both the five-helix domain (CCM2cts) and the following C-terminal tail. The end of the C-terminal tail forms an isolated helix, which interacts intramolecularly with CCM2cts. By biochemical studies we identified the N-terminal amphiphilic helix of MEKK3 (MEKK3-nhelix) as the essential structural element for CCM2ct binding. We further determined the crystal structure of CCM2cts-MEKK3-nhelix complex, in which MEKK3-nhelix binds to the same site of CCM2cts for CCM2ct intramolecular interaction. These findings build a structural framework for understanding CCM2ct-MEKK3 molecular recognition.

Structural Insights into the Molecular Recognition between Cerebral Cavernous Malformation 2 and Mitogen-Activated Protein Kinase Kinase Kinase 3.,Wang X, Hou Y, Deng K, Zhang Y, Wang DC, Ding J Structure. 2015 Apr 29. pii: S0969-2126(15)00131-8. doi:, 10.1016/j.str.2015.04.003. PMID:25982527^[5]

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

References

↑ Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U. Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative. J Biol Chem. 1997 Jan 31;272(5):2668-74. PMID:9006902
↑ Nakamura K, Johnson GL. PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway. J Biol Chem. 2003 Sep 26;278(39):36989-92. Epub 2003 Aug 11. PMID:12912994 doi:http://dx.doi.org/10.1074/jbc.C300313200
↑ Huang Q, Yang J, Lin Y, Walker C, Cheng J, Liu ZG, Su B. Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nat Immunol. 2004 Jan;5(1):98-103. Epub 2003 Dec 7. PMID:14661019 doi:http://dx.doi.org/10.1038/ni1014
↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004 Feb;6(2):97-105. Epub 2004 Jan 25. PMID:14743216 doi:http://dx.doi.org/10.1038/ncb1086
↑ Wang X, Hou Y, Deng K, Zhang Y, Wang DC, Ding J. Structural Insights into the Molecular Recognition between Cerebral Cavernous Malformation 2 and Mitogen-Activated Protein Kinase Kinase Kinase 3. Structure. 2015 Apr 29. pii: S0969-2126(15)00131-8. doi:, 10.1016/j.str.2015.04.003. PMID:25982527 doi:http://dx.doi.org/10.1016/j.str.2015.04.003

1 Structural highlights
2 Disease
3 Function
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/4yl6"

Categories: Ding, J | Wang, D C | Wang, X | Adaptor-partner complex | Protein binding

@@ Line 1: / Line 1: @@
 ==Crystal structure of truncated cerebral cavernous malformation 2 C-terminal adaptor domain in complex with an internal helix of mitogen-activated protein kinase kinase kinase 3==
 <StructureSection load='4yl6' size='340' side='right' caption='[[4yl6]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4yl6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YL6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YL6 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ykc|4ykc]], [[4ykd|4ykd]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yl6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yl6 RCSB], [http://www.ebi.ac.uk/pdbsum/4yl6 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yl6 OCA], [http://pdbe.org/4yl6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yl6 RCSB], [http://www.ebi.ac.uk/pdbsum/4yl6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yl6 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4yl6" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4yl6

From Proteopedia

Revision as of 17:05, 22 March 2017

Crystal structure of truncated cerebral cavernous malformation 2 C-terminal adaptor domain in complex with an internal helix of mitogen-activated protein kinase kinase kinase 3

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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