4N1D

Nodal/BMP2 chimera NB250

Summary for 4N1D

• Entry DOI: 10.2210/pdb4n1d/pdb
• Descriptor: Nodal/BMP2 chimera protein (2 entities in total)
• Functional Keywords: cytokine, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P12643
• Total number of polymer chains: 1
• Total formula weight: 13584.69

Authors

Esquivies, L. (deposition date: 2013-10-04, release date: 2013-12-04, Last modification date: 2024-10-30)

Primary citation

Esquivies, L.,Blackler, A.,Peran, M.,Rodriguez-Esteban, C.,Izpisua Belmonte, J.C.,Booker, E.,Gray, P.C.,Ahn, C.,Kwiatkowski, W.,Choe, S.
Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure.
J.Biol.Chem., 289:1788-1797, 2014

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.

PubMed: 24311780
DOI: 10.1074/jbc.M113.529180

Experimental method

X-RAY DIFFRACTION (1.912 Å)