3ENM

The structure of the MAP2K MEK6 reveals an autoinhibitory dimer

Summary for 3ENM

• Entry DOI: 10.2210/pdb3enm/pdb
• Descriptor: Dual specificity mitogen-activated protein kinase kinase 6, SULFATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: mek6, autoinhibited dimer, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, tyrosine-protein kinase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 147194.66

Authors

Min, X.,Akella, R.,He, H.,Humphreys, J.M.,Tsutakawa, S.,Lee, S.-J.,Tainer, J.A.,Cobb, M.H.,Goldsmith, E.J. (deposition date: 2008-09-25, release date: 2009-03-03, Last modification date: 2024-11-13)

Primary citation

Min, X.,Akella, R.,He, H.,Humphreys, J.M.,Tsutakawa, S.E.,Lee, S.J.,Tainer, J.A.,Cobb, M.H.,Goldsmith, E.J.
The structure of the MAP2K MEK6 reveals an autoinhibitory dimer
Structure, 17:96-104, 2009

PubMed Abstract: MAP2Ks are dual-specificity protein kinases functioning at the center of three-tiered MAP kinase modules. The structure of the kinase domain of the MAP2K MEK6 with phosphorylation site mimetic aspartic acid mutations (MEK6/DeltaN/DD) has been solved at 2.3 angstroms resolution. The structure reveals an autoinhibited elongated ellipsoidal dimer. The enzyme adopts an inactive conformation, based upon structural queues, despite the phosphomimetic mutations. Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/DeltaN/DD and full-length unphosphorylated wild-type MEK6 in solution. The interface includes the phosphate binding ribbon of each subunit, part of the activation loop, and a rare "arginine stack" between symmetry-related arginine residues in the N-terminal lobe. The autoinhibited structure likely confers specificity on active MAP2Ks. The dimer may also serve the function in unphosphorylated MEK6 of preventing activation loop phosphorylation by inappropriate kinases.

PubMed: 19141286
DOI: 10.1016/j.str.2008.11.007

Experimental method

X-RAY DIFFRACTION (2.35 Å)