Related Experiment Video
Updated: Jun 26, 2026

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
Published on: July 19, 2024
The structure of the MAP2K MEK6 reveals an autoinhibitory dimer
Xiaoshan Min1, Radha Akella, Haixia He
1Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816, USA.
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.
Related Concept Videos
MAPK Signaling Cascades
Microtubule Associated Proteins (MAPs)
Structure of Benzene: Kekulé Model
He proposed that benzene has a cyclic structure of six carbon atoms attached to one hydrogen atom each, with three alternating pi bonds.
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...

