4n1d

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Nodal/BMP2 chimera NB250Nodal/BMP2 chimera NB250

Structural highlights

4n1d is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.912Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NODAL_HUMAN Alobar holoprosencephaly;Situs ambiguus;Lobar holoprosencephaly;Semilobar holoprosencephaly;Midline interhemispheric variant of holoprosencephaly;Septopreoptic holoprosencephaly;Situs inversus totalis;Microform holoprosencephaly. The disease is caused by variants affecting the gene represented in this entry.

Function

NODAL_HUMAN Essential for mesoderm formation and axial patterning during embryonic development.BMP2_HUMAN Induces cartilage and bone formation.

Publication Abstract from PubMed

Nodal, a member of the TGF-beta 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.

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 JC, Booker E, Gray PC, Ahn C, Kwiatkowski W, Choe S J Biol Chem. 2014 Jan 17;289(3):1788-97. doi: 10.1074/jbc.M113.529180. Epub 2013 , Dec 5. PMID:24311780[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Esquivies L, Blackler A, Peran M, Rodriguez-Esteban C, Izpisua Belmonte JC, Booker E, Gray PC, Ahn C, Kwiatkowski W, Choe S. Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure. J Biol Chem. 2014 Jan 17;289(3):1788-97. doi: 10.1074/jbc.M113.529180. Epub 2013 , Dec 5. PMID:24311780 doi:http://dx.doi.org/10.1074/jbc.M113.529180

4n1d, resolution 1.91Å

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OCA