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J Biol Chem. 2014 Jan 17;289(3):1788-97. doi: 10.1074/jbc.M113.529180. Epub 2013 Dec 5.

Designer nodal/BMP2 chimeras mimic nodal signaling, promote chondrogenesis, and reveal a BMP2-like structure.

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1
From the Structural Biology Laboratory.

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.

KEYWORDS:

Bone Morphogenetic Protein (BMP); Cartilage Biology; Chondrogenesis; Nodal; Protein Chimeras; Protein Structure

PMID:
24311780
PMCID:
PMC3894355
DOI:
10.1074/jbc.M113.529180
[Indexed for MEDLINE]
Free PMC Article
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