4yl6

From Proteopedia

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

PDB ID 4yl6

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Structural highlights

4yl6 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 2.1Å
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).

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^[1]

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

References

↑ 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