An unusual feature revealed by the crystal structure at 2.2 Å resolution of human transforming growth fact or-β2
Abstract
TRANSFORMING growth factor type β (TGF-β2)1 is a member of an expanding family of growth factors that regulate prolifer-ation and differentiation of many different cell types2,3. TGF-β2 binds to various receptors4, one of which was shown to be a serine/threonine kinase5. TGF-β2 is involved in wound healing6, bone formation7 and modulation of immune functions8. We report here the crystal structure of TGF-β2 at 2.2 Å resolution, which reveals a novel monomer fold and dimer association. The monomer consists of two antiparallel pairs of β-strands forming a flat curved surface and a separate, long α-helix. The disulphide-rich core has one disulphide bond pointing through a ring formed by the sequence motifs Cys-Ala-Gly-Ala-Cys and Cys-Lys-Cys, which are themselves connected through the cysteines. Two monomers are connected through a single disulphide bridge and associate such that the helix of one subunit interacts with the concave β-sheet surface of the other. Four exposed loop regions might determine receptor specificity. The structure provides a suitable model for the TGF-βs and other members of the super-family9-11 and is the basis for the analysis of the TGF-β2 interactions with the receptor.
- Publication:
-
Nature
- Pub Date:
- July 1992
- DOI:
- 10.1038/358430a0
- Bibcode:
- 1992Natur.358..430S