Literature summary for 2.7.11.25 extracted from

Wang, X.; Hou, Y.; Deng, K.; Zhang, Y.; Wang, D.C.; Ding, J.
Structural insights into the molecular recognition between cerebral cavernous malformation 2 and mitogen-activated protein kinase kinase kinase 3 (2015), Structure, 23, 1087-1096.

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Protein Variants

Protein Variants	Comment	Organism
D13A	site-directed mutagenesis, the mutation of the conserved Asp13 of MEKK3 to Ala completely abolishes the binding between CCM2ct and MEKK3nt	Homo sapiens
E3A	site-directed mutagenesis, the mutation of the nonconserved Glu3 of MEKK3 to Ala causes a 2fold reduction of the binding affinity between CCM2ct and MEKK3nt	Homo sapiens
I10D	site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt	Homo sapiens
K14D	site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt	Homo sapiens
K17D	site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt	Homo sapiens
K7D	site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q99759	-	-

Synonyms

Synonyms	Comment	Organism
MEKK3	-	Homo sapiens
mitogen-activated protein kinase kinase kinase 3	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	on mutating either of the four crucial hydrophobic residues (Leu7, Ile10, Leu14, and Leu17) to charged Asp or substituting the conserved Asp13 to Ala in MEKK3, the binding between CCM2ct and MEKK3nt is completely abolished. Mutation of the nonconserved Glu3 of MEKK3 to Ala induced only 2fold reduction of the binding affinity between CCM2ct and MEKK3nt	Homo sapiens
additional information	structural insights into the molecular recognition between cerebral cavernous malformation 2 (CCM2) and mitogen-activated protein kinase kinase kinase 3 (MEKK3): CCM2 functions as an adaptor protein that mediates the activation of MEKK3 signaling in response to osmotic stress, or negatively regulates MEKK3 signaling, which is important for normal cardiovascular development. CCM2ct assembles into a global six-helix domain by intramolecular interaction, CCM2ct intramolecular interaction is weak. The N-terminal amphiphilic helix of MEKK3 (MEKK3-n_helix) as the essential structural element for CCM2ct binding, CCM2ct directly interacts with MEKK3 N-terminal helix. The binding of CCM2ct to MEKK3-n_helix resembles CCM2ct intramolecular interaction, surface plasmon resonance, analysis, overview. Determinative roles of MEKK3 residues Leu7, Ile10, Leu14, and Leu17 and auxiliary role for residue Glu3 in CCM2ct-MEKK3 recognition by mutational analysis. The resulting CCM2-MEKK3 interaction builds a molecular platform for regulating MEKK3 signaling	Homo sapiens
physiological function	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	Homo sapiens

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Release 2023.1 (January 2023)