The solution structure of the disulphide-linked homodimer of the human trefoil protein TFF1.
The trefoil factor family protein, TFF1, forms a homodimer, via a disulphide linkage, that has greater activity in wound healing assays than the monomer. Having previously determined a high-resolution solution structure of a monomeric analogue of TFF1, we now investigate the structure of the homodimer formed by the native sequence. The two putative receptor/ligand recognition domains are found to be well separated, at opposite ends of a flexible linker. This contrasts sharply with the known fixed and compact arrangement of the two trefoil domains of the closely related TFF2, and has significant implications for the mechanism of action and functional specificity of the TFF of proteins.
Williams
M A
MA
Molecular Structure Division, National Institute for Medical Research, Mill Hill London NW7 1AA, UK. m.williams@biochemistry.ucl.ac.uk
Westley
B R
BR
May
F E
FE
Feeney
J
J
D000595:Amino Acid Sequence; D002118:Calcium / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D006133:Growth Substances / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012996:Solutions; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins
D004220:Disulfides; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D012996:Solutions; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D003545:Cysteine; D002118:Calcium