title: An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2.
abstract: Transforming growth factor type beta 2 (TGF-beta 2) is a member of an expanding family of growth factors that regulate proliferation and differentiation of many different cell types. TGF-beta 2 binds to various receptors, one of which was shown to be a serine/threonine kinase. TGF-beta 2 is involved in wound healing, bone formation and modulation of immune functions. We report here the crystal structure of TGF-beta 2 at 2.2 A resolution, which reveals a novel monomer fold and dimer association. The monomer consists of two antiparallel pairs of beta-strands forming a flat curved surface and a separate, long alpha-helix. The disulphide-rich core has one disulphide bone 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 beta-sheet surface of the other. Four exposed loop regions might determine receptor specificity. The structure provides a suitable model for the TGF-beta s and other members of the super-family and is the basis for the analysis of the TGF-beta 2 interactions with the receptor.
authors.affiliation: Department of Biotechnology, Pharmaceuticals Division, Ciba-Geigy, Basel, Switzerland.
authors.forename: M P
authors.initials: MP
authors.lastname: Schlunegger
authors.forename: M G
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003196:Computer Graphics; D003461:Crystallography; D004220:Disulfides; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins; D012997:Solvents; D016212:Transforming Growth Factor beta / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004220:Disulfides; D011994:Recombinant Proteins; D012997:Solvents; D016212:Transforming Growth Factor beta