4N1D

Nodal/BMP2 chimera NB250


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.91 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.178 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure.

Esquivies, L.Blackler, A.Peran, M.Rodriguez-Esteban, C.Izpisua Belmonte, J.C.Booker, E.Gray, P.C.Ahn, C.Kwiatkowski, W.Choe, S.

(2014) J Biol Chem 289: 1788-1797

  • DOI: https://doi.org/10.1074/jbc.M113.529180
  • Primary Citation of Related Structures:  
    4N1D

  • PubMed Abstract: 

    Nodal, a member of the TGF-β superfamily, plays an important role in vertebrate and invertebrate early development. The biochemical study of Nodal and its signaling pathway has been a challenge, mainly because of difficulties in producing the protein in sufficient quantities. We have developed a library of stable, chemically refoldable Nodal/BMP2 chimeric ligands (NB2 library). Three chimeras, named NB250, NB260, and NB264, show Nodal-like signaling properties including dependence on the co-receptor Cripto and activation of the Smad2 pathway. NB250, like Nodal, alters heart looping during the establishment of embryonic left-right asymmetry, and both NB250 and NB260, as well as Nodal, induce chondrogenic differentiation of human adipose-derived stem cells. This Nodal-induced differentiation is shown to be more efficient than BPM2-induced differentiation. Interestingly, the crystal structure of NB250 shows a backbone scaffold similar to that of BMP2. Our results show that these chimeric ligands may have therapeutic implications in cartilage injuries.


  • Organizational Affiliation

    From the Structural Biology Laboratory.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nodal/BMP2 chimera protein116Homo sapiensMutation(s): 0 
Gene Names: BMP2BMP2ANodal
UniProt & NIH Common Fund Data Resources
Find proteins for Q96S42 (Homo sapiens)
Explore Q96S42 
Go to UniProtKB:  Q96S42
PHAROS:  Q96S42
GTEx:  ENSG00000156574 
Find proteins for P12643 (Homo sapiens)
Explore P12643 
Go to UniProtKB:  P12643
PHAROS:  P12643
GTEx:  ENSG00000125845 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsQ96S42P12643
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.91 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.178 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.57α = 90
b = 95.57β = 90
c = 97.494γ = 120
Software Package:
Software NamePurpose
SCALAdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
XDSdata reduction
MrBUMPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-04
    Type: Initial release
  • Version 1.1: 2014-02-05
    Changes: Database references
  • Version 1.2: 2017-07-26
    Changes: Refinement description, Source and taxonomy