Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation

Juyoux P, Galdadas I, Gobbo D, von Velsen J, Pelosse M, Tully M, Vadas O, Gervasio F, Pellegrini E, Bowler M, Science 381(6663):1217-1225 (2023) DOI

SASDRD6 – Dual specificity mitogen-activated protein kinase kinase 6 (MKK6GRA) bound to mitogen-activated protein kinase 14 (p38α) with AMP-PCP

Mitogen-activated protein kinase 14
Dual specificity mitogen-activated protein kinase kinase 6
5′‐adenylyl methylenediphosphonate
MWexperimental 68 kDa
MWexpected 83 kDa
VPorod 116 nm3
log I(s) 2.99×10-1 2.99×10-2 2.99×10-3 2.99×10-4
Mitogen-activated protein kinase 14 Dual specificity mitogen-activated protein kinase kinase 6 5′‐adenylyl methylenediphosphonate small angle scattering data  s, nm-1
ln I(s)
Mitogen-activated protein kinase 14 Dual specificity mitogen-activated protein kinase kinase 6 5′‐adenylyl methylenediphosphonate Guinier plot ln 2.99×10-1 Rg: 4.2 nm 0 (4.2 nm)-2 s2
(sRg)2I(s)/I(0)
Mitogen-activated protein kinase 14 Dual specificity mitogen-activated protein kinase kinase 6 5′‐adenylyl methylenediphosphonate Kratky plot 1.104 0 3 sRg
p(r)
Mitogen-activated protein kinase 14 Dual specificity mitogen-activated protein kinase kinase 6 5′‐adenylyl methylenediphosphonate pair distance distribution function Rg: 4.0 nm 0 Dmax: 14.0 nm

Data validation


There are no models related to this curve.

Synchrotron SAXS data from solutions of the MKK6GRA-p38α complex with AMP-PCP in 50 mM HEPES, 200 mM NaCl, 10 mM MgCl2, 5 % glycerol, 0.5 mM TCEP, pH 7.5 were collected on the B21 beam line at the Diamond Light Source (Didcot, UK) using a Eiger 4M detector at a sample-detector distance of 3.7 m and at a wavelength of λ = 0.1 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 5.00 mg/ml was measured at 20°C. 10 successive 1 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

AMP-PCP ia an adenosine triphosphate analogue: https://pubchem.ncbi.nlm.nih.gov/compound/AMP-PCP-_disodium

Mitogen-activated protein kinase 14 (p38α, WT)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Monomer
Mon. MW   40.5 kDa
 
UniProt   Q16539 (10-360)
Sequence   FASTA
 
Dual specificity mitogen-activated protein kinase kinase 6 (MKK6DDGRA)
Mol. type   Protein
Organism   synthetic construct
Olig. state   Monomer
Mon. MW   41.8 kDa
Sequence   FASTA
 
5′‐adenylyl methylenediphosphonate (AMP-PCP)
Mol. type   Other
Olig. state   Monomer
Mon. MW   0.5 kDa
Chemical formula