Transforming growth factor β1: Three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor β2

Andrew P. Hinck, Sharon J. Archer, Su Wen Qian, Anita B. Roberts, Michael B. Sporn, James A. Weatherbee, Monica L.S. Tsang, Roger Lucas, Bo Ling Zhang, Jeff Wenker, Dennis A. Torchia

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


The three-dimensional solution structure of human transforming growth factor β1 (TGF-β1) has been determined using multinuclear magnetic resonance spectroscopy and a hybrid distance geometry/simulated annealing algorithm. It represents one of the first examples of a mammalian protein structure that has been solved by isotopic labeling of the protein in a eukaryotic cell line and multinuclear NMR spectroscopy. The solution structure of the 25 kDa disulfide-linked TGF-β1 homodimer was calculated from over 3200 distance and dihedral angle restraints. The final ensemble of 33 accepted structures had no NOE or dihedral angle violations greater than 0.30 Å and 5.0°, respectively. The RMSD of backbone atoms for the ensemble of 33 structures relative to their mean structure was 1.1 Å when all residues were used in the alignment and 0.7 Å when loop regions were omitted. The solution structure of TGF-β1 follows two independently determined crystal structures of TGF-β2 (Daopin et al., 1992, 1993; Schlunegger and Grutter, 1992, 1993), providing the first opportunity to examine structural differences between the two isoforms at the molecular level. Although the structures are very similar, with an RMSD in backbone atom positions of 1.4 Å when loop regions are omitted in the alignment and 1.9 Å when all residues are considered, there are several notable differences in structure and flexibility which may be related to function. The clearest example of these is in the β-turn from residues 69-72: the turn type found in the solution structure of TGF-β1 falls into the category of type II, whereas that present in the X-ray crystal structure of TGF-β2 is more consistent with a type I turn conformation. This may be of functional significance as studies using TGF-β chimeras and deletion mutants indicate that this portion of the molecule may be important in receptor binding.

Original languageEnglish (US)
Pages (from-to)8517-8534
Number of pages18
Issue number26
StatePublished - Aug 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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