Trefoil proteins

Fig. 3. Representation of the nine principal folds which recur in protein stmctures, where the codes of the representative proteins taken from the Brookhaven Protein Data Bank (PDB) (17) are given in parentheses (18) (1) globin (Ithb) (2) trefoil (lilb) (3) up—down (256b) (4) immunoglobulin folds...

Mucins are also thought to act in cooperation with trefoil proteins in the protection and repair of the epithelium (Kindon et al., 1995). Trefoil factors are expressed along the GI tract and increased levels are noted near sites of inflammation and ulcerative lesions (Babyatsky et al., 1996). Furthermore, it has been demonstrated that mouse intestinal trefoil factor may play a role in the alteration of the physicochemical nature of GC mucins during N. brasiliensis infection (Tomita et al., 1995). Perhaps in GI nematode parasite infection mucins are not aiding in the host s protective expulsion of the parasite, but rather are functioning in the repair of the damaged intestinal epithelium. 

Members of the trefoil factor family of small proteins are solid candidates to be mucin interchain cross-linkers (Otto and Thim 2005). For example, TFF1 is mainly expressed in the goblet cells of gastric mucosa, where it co-localizes with and binds to MUC5AC (Ruchaud-Sparagano et al. 2004). Yeast two-hybrid... 

Otte J.M., Kiehne K. and Herzig K.H. (2003) Antimicrobial peptides in innate immunity of the human intestine. J Gastoenterol 38, 717-726 Otto W.R. and Thim L. (2005) Trefoil factor family-interacting proteins. Cell Mol Life Sci. 62, 2939-2946... 

Trefoil factor family peptides, (TFF peptides), secretory mucin-associated peptides (trefoil peptides) largely found in ep-ithelia of the gastrointestinal tract. They share the TFF domain, a Cys-rich protein module with a consensus structure of 42 amino acids and six conserved Cys residues forming three intramolecular disulfide bridges between Cys -Cys, Cys -Cys, and Cys -Cys ". The TFF pep-... 

Orthogonal P-sheet proteins. An alternative way of packing two P-sheets together is with the strands in the two sheets almost perpendicular in a trefoil superfold. Each domain of the serine proteases (e.g. trypsin. Figure 5.10D) shows this arrangement. 

The answer is positive yes, there are proteins with knots. Sometimes, these are simple trefoil knots, but a few cases are known with rather complex... 

Knots can of course be addressed also for toy lattice proteins discussed in section 10.10. The shortest cubic lattice knot has 24 monomers (Figure C11.7 a), but it is not space filling. The shortest space filling (open ended) lattice polymer to have knot is 36-mer. Its conformation with a trefoil knot is shown in the Figure C11.7. By the way, if the sequence of monomer species in it is properly selected (see Section 10.6), it folds in virtuo, of course) quite successfully, and not much slower that the corresponding chain without a knot — which opens even wider the question as to why real proteins are statistically less likely to have knots than random. 

As their name implies, these molecules are characterised by their distinctive topology in which the macrocycle is intertwined to form a knot [170, 171]. The simplest form of knot is the so-called trefoil knot - trefoil as in tracery or heraldry, in turn derived from tripartite leaves, as in clover (which of course is not knotted ). More complex forms are found throughout chemistry and physics [318] and in Nature - in proteins [319], metalloproteins [320] and DNA (both natural [321], and in synthetic derivatives [322]). However not all structures claimed to be knots conform to the strict mathematical definition of a knot (Section 4.2.1). 

Fig. 8.3 The degradation of the large subunit (LSU) and small subunit (SSU) of ribulose-l,5-bis-phosphate carboxylase/oxygenase (Ruhisco) during in vitro incubation of toted ieeif protein extracted from white clover (Trifolium repens) with Streptococcus bovis rumen bacteried strrdns (105 cells innoculated) and condensed tannins extracted from Lotus comicidatus (birdsfoot trefoil). Incubations were performed with (b, CT-active) and without CT (a, CT-inactive). Sampies were removed prior (0 h) and after 2, 4, 8, 12, and 24 h of incubation. The sample on the left side of each gel contains the broad range molecular weight (MW) markers (Bio-RAD, Hercules, CA Min, 2012, unpublished data)...

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