Toggle Main Menu Toggle Search

Open Access padlockePrints

The closely related estrogen-regulated trefoil proteins TFF1 and TFF3 have markedly different hydrodynamic properties, overall charge, and distribution of surface charge

Lookup NU author(s): Dr Felicity May, Dr Stephen Church, Professor Bruce Westley


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


The human trefoil proteins TFF1 and TFF3 are expressed predominantly in the gastrointestinal tract. They are also expressed and regulated by estrogens in malignant breast epithelial cells. TFF1 and TFF3 are small cysteine-rich acidic secreted proteins of 60 and 59 amino acids with similar isoelectric points of 4.75 and 3.94, respectively. Each contains one trefoil domain that is characterized by several conserved features including six cysteine residues with conserved spacing. TFF1 and TFF3 form intermolecular disulfide bonds via an extra-trefoil domain cysteine residue and are present in vivo as monomers and homodimers and as complexes with other proteins. The TFF1 dimer is more active than the TFF1 monomer. In the present study the hydrodynamic and charge properties of TFF1 and TFF3 monomers and homodimers have been compared and shown to differ markedly. Notably, TFF1 is significantly more asymmetric than TFF3 (frictional coefficients 1.25 and 1.12, respectively, p < 0.001), and homodimerization of TFF1 results in a greater increase in asymmetry than for TFF3. The overall charges of TFF1 and TFF3 are very different at neutral pH. Titration curves predicted significant differences in charge across a wide pH range that agreed well with experimental data. The locations of charged amino acids in the primary sequences and in the tertiary structures of TFF1 and TFF3 were examined. This revealed interesting divergence in both the distribution and local topology of charged amino acid side chains. The significant differences between the shape, size, and surface charge of these two closely related molecules may account for their divergent biological activities.

Publication metadata

Author(s): May FEB, Church S, Major S, Westley BR

Publication type: Article

Publication status: Published

Journal: Biochemistry

Year: 2003

Volume: 42

Issue: 27

Pages: 8250-8259

Print publication date: 15/07/2003

ISSN (print): 0006-2960

ISSN (electronic): 1943-295X


DOI: 10.1021/bi030025l

PubMed id: 12846574


Altmetrics provided by Altmetric