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An unusual feature revealed by the crystal structure at 2.2 Å resolution of human transforming growth fact or-β2

Nature volume 358, pages 430–434 (1992)Cite this article

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.

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  1. Department of Biotechnology, Pharmaceuticals Division, Ciba-Geigy, CH-4002, Basel, Switzerland

    Michael P. Schlunegger & Markus G. Grütter

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  1. Michael P. Schlunegger
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  2. Markus G. Grütter
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Schlunegger, M., Grütter, M. An unusual feature revealed by the crystal structure at 2.2 Å resolution of human transforming growth fact or-β2. Nature 358, 430–434 (1992). https://doi.org/10.1038/358430a0

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