4UX9

Crystal structure of JNK1 bound to a MKK7 docking motif


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.34 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure and Dynamics of the Mkk7-Jnk Signaling Complex.

Kragelj, J.Palencia, A.Nanao, M.H.Maurin, D.Bouvignies, G.Blackledge, M.Jensen, M.R.

(2015) Proc Natl Acad Sci U S A 112: 3409

  • DOI: https://doi.org/10.1073/pnas.1419528112
  • Primary Citation of Related Structures:  
    4UX9

  • PubMed Abstract: 

    Signaling specificity in the mitogen-activated protein kinase (MAPK) pathways is controlled by disordered domains of the MAPK kinases (MKKs) that specifically bind to their cognate MAPKs via linear docking motifs. MKK7 activates the c-Jun N-terminal kinase (JNK) pathway and is the only MKK containing three motifs within its regulatory domain. Here, we characterize the conformational behavior and interaction mechanism of the MKK7 regulatory domain. Using NMR spectroscopy, we develop an atomic resolution ensemble description of MKK7, revealing highly diverse intrinsic conformational propensities of the three docking sites, suggesting that prerecognition sampling of the bound-state conformation is not prerequisite for binding. Although the different sites exhibit similar affinities for JNK1, interaction kinetics differ considerably. Importantly, we determine the crystal structure of JNK1 in complex with the second docking site of MKK7, revealing two different binding modes of the docking motif correlating with observations from NMR exchange spectroscopy. Our results provide unique insight into how signaling specificity is regulated by linear motifs and, in general, into the role of conformational disorder in MAPK signaling.


  • Organizational Affiliation

    Université Grenoble Alpes, Centre National de la Recherche Scientifique, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, F-38044 Grenoble, France; and.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MITOGEN-ACTIVATED PROTEIN KINASE 8
A, B, C, D
364Homo sapiensMutation(s): 0 
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P45983 (Homo sapiens)
Explore P45983 
Go to UniProtKB:  P45983
PHAROS:  P45983
GTEx:  ENSG00000107643 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45983
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 7E [auth F],
F [auth G],
G [auth H],
H [auth I]
12Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O14733 (Homo sapiens)
Explore O14733 
Go to UniProtKB:  O14733
PHAROS:  O14733
GTEx:  ENSG00000076984 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14733
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ANP
Query on ANP

Download Ideal Coordinates CCD File 
I [auth A],
N [auth B],
S [auth C],
X [auth D]
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER
C10 H17 N6 O12 P3
PVKSNHVPLWYQGJ-KQYNXXCUSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
AA [auth D]
BA [auth H]
J [auth A]
K [auth A]
L [auth A]
AA [auth D],
BA [auth H],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
O [auth B],
P [auth B],
Q [auth B],
R [auth B],
T [auth C],
U [auth C],
V [auth C],
W [auth C],
Y [auth D],
Z [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.34 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 108.666α = 90
b = 180.159β = 110.3
c = 101.144γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-25
    Type: Initial release
  • Version 1.1: 2016-04-06
    Changes: Database references
  • Version 1.2: 2017-09-27
    Changes: Data collection
  • Version 1.3: 2020-08-19
    Changes: Derived calculations, Other
  • Version 1.4: 2024-01-10
    Changes: Data collection, Database references, Refinement description