title: Sequence-specific 1H-NMR assignments and identification of two small antiparallel beta-sheets in the solution structure of recombinant human transforming growth factor alpha.
abstract: Transforming growth factor alpha (TGF alpha) is a small mitogenic protein with about 35% sequence identity with epidermal growth factor (EGF). TGF alpha-like proteins have been proposed to play a role in oncogenesis and wound healing. This report describes sequence-specific 1H-NMR resonance assignments for recombinant human TGF alpha (hTGF alpha). These assignments provide the basis for interpreting NMR data which demonstrate that the solution structure of hTGF alpha includes an antiparallel beta-sheet involving residues Gly-19 to Leu-24 and Lys-29 to Cys-34 and a second, smaller, antiparallel beta-sheet involving residues Tyr-38 and Val-39 and His-45 and Ala-46. These data, together with constraints imposed by the disulfide bonds, are combined to construct a molecular model of the polypeptide chain fold for residues Cys-8 to Ala-46. The resulting structure is similar to that of mouse and human EGF. Human TGF alpha and mouse EGF, however, differ with respect to their structural dynamics, since amide proton/deuteron exchange is much faster for hTGF alpha than for mouse EGF at pH 3.5.
authors.affiliation: Biophysics Research Division, University of Michigan, Ann Arbor 48109.
authors.forename: G T
authors.initials: GT
authors.lastname: Montelione
authors.forename: M E
authors.initials: ME
authors.lastname: Winkler
authors.forename: L E
authors.initials: LE
authors.lastname: Burton
authors.forename: E
authors.initials: E
authors.lastname: Rinderknecht
authors.forename: M B
authors.initials: MB
authors.lastname: Sporn
authors.forename: G
authors.initials: G
authors.lastname: Wagner
mesh_terms: D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011487:Protein Conformation; D011994:Recombinant Proteins; D012996:Solutions; D015291:Transforming Growth Factors / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D012996:Solutions; D015291:Transforming Growth Factors; D006859:Hydrogen