RCSB PDB - 4NIF: Heterodimeric structure of ERK2 and RSK1

 4NIF

Heterodimeric structure of ERK2 and RSK1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.161 

Starting Models: experimental
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Ligand Structure Quality Assessment 

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This is version 1.3 of the entry. See complete history


Literature

Structural assembly of the signaling competent ERK2-RSK1 heterodimeric protein kinase complex

Alexa, A.Gogl, G.Glatz, G.Garai, A.Zeke, A.Varga, J.Dudas, E.Jeszenoi, N.Bodor, A.Hetenyi, C.Remenyi, A.

(2015) Proc Natl Acad Sci U S A 112: 2711-2716

  • DOI: https://doi.org/10.1073/pnas.1417571112
  • Primary Citation of Related Structures:  
    4NIF

  • PubMed Abstract: 

    Mitogen-activated protein kinases (MAPKs) bind and activate their downstream kinase substrates, MAPK-activated protein kinases (MAPKAPKs). Notably, extracellular signal regulated kinase 2 (ERK2) phosphorylates ribosomal S6 kinase 1 (RSK1), which promotes cellular growth. Here, we determined the crystal structure of an RSK1 construct in complex with its activator kinase. The structure captures the kinase-kinase complex in a precatalytic state where the activation loop of the downstream kinase (RSK1) faces the enzyme's (ERK2) catalytic site. Molecular dynamics simulation was used to show how this heterodimer could shift into a signaling-competent state. This structural analysis combined with biochemical and cellular studies on MAPK→MAPKAPK signaling showed that the interaction between the MAPK binding linear motif (residing in a disordered kinase domain extension) and the ERK2 "docking" groove plays the major role in making an encounter complex. This interaction holds kinase domains proximal as they "readjust," whereas generic kinase domain surface contacts bring them into a catalytically competent state.


  • Organizational Affiliation

    Lendület Protein Interaction Group, Institute of Enzymology, Research Centre for Natural Sciences, and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ribosomal protein S6 kinase alpha-1A,
C [auth D]
333Homo sapiensMutation(s): 0 
Gene Names: RPS6KA1MAPKAPK1ARSK1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q15418 (Homo sapiens)
Explore Q15418 
Go to UniProtKB:  Q15418
PHAROS:  Q15418
GTEx:  ENSG00000117676 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15418
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 1B,
D [auth E]
362Homo sapiensMutation(s): 0 
Gene Names: MAPK1ERK2PRKM1PRKM2
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P28482 (Homo sapiens)
Explore P28482 
Go to UniProtKB:  P28482
PHAROS:  P28482
GTEx:  ENSG00000100030 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28482
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ANP
Query on ANP

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

Download Ideal Coordinates CCD File 
F [auth B],
G [auth B],
J [auth E]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
NA
Query on NA

Download Ideal Coordinates CCD File 
H [auth B],
K [auth E]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.161 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.49α = 90
b = 87.85β = 108.22
c = 116.54γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted ANPClick on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-11-12
    Type: Initial release
  • Version 1.1: 2015-03-04
    Changes: Database references
  • Version 1.2: 2015-03-25
    Changes: Database references
  • Version 1.3: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description