Fibronectin type III

Figure 13.19 Ribbon diagram of the stmcture of the extracellular domain of the human growth hormone. The hormone-binding region is formed by loops (yellow) at the hinge region between two fibronectin type III domains. (Adapted from J. Wells et al., Annu. Rev.

Figure 15.24 Ribbon diagram (a) and topology diagram (b) of the fibronectin type III domain, which is composed of a three-stranded and a four-stranded p sheet packed together as a compressed barrel.

Adhesion proteins in this group contain an immunoglobulin domain that is composed of 90-100 amino acids arranged in a sandwich of two sheets of antiparallei strands. Some members of this family also contain fibronectin type III—like domains in addition to the immunoglobulin domain. Immunoglobulin-related adhesion proteins either can exist as transmembrane structures or can be attached to cell membranes via glycosyl phosphatidylinositol links (B4, R5). 

Erickson HP. Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. Proc Natl Acad Sci USA 1994 91 10114-10118. 

From Guss and Freeman.116 (B) Ribbon drawing of immunoglobulin fold. This is a common structure in domains of the immunoglobulins and in many other extracellular proteins. Two layers of antiparallel (3 sheet are stacked face to face to form a flattened barrel. One disulfide bridge is always present and is represented as a thick rod. From J. Richardson.117 (C) Five tandem fibronectin type III domains. 

Q Fibronectin type III domain (motif I) Q MLCK region [] Immunoglobulin domain (motif II) Q Interdomain... 

Plaxco, K.W., Spitzfaden, C., Campbell, I.D. and Dobson, C.M. (1997) A comparison of the folding kinetics and thermodynamics of two homologous fibronectin type III modules. Journal of Molecular Biology 270,... 

Leahy, D. J., Hendrickson, W. A., Aukhil, L, and Erickson, H. P. (1992). Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the seleno-methionyl protein. Science 258, 987-991. 

The extracellular portion of the hGHR and PRLR receptors is composed of two canonical fibronectin type III (FNIII) /3-sheet modules (Fig. 2). The N- and G-terminal domains each contain about 110 amino acids of very similar structures that are connected by a 5-6 residue linker (De Vos et al, 1992 Somers et al, 1994). However, the interdomain angles between the N and G-terminal domains differ substantially between the... 

Bonaldo P, Colombatti A The carboxyl terminus offiie chickoi o3 chain of ocdlagen VI is a unique mosaic structure with glycoprotein Ib-like, fibronectin type III and Kunitz modules. J Biol Chon 264 20235-20239,1989... 

Steward, A., Adhya, S., Clarke, J. Sequence conservation in Ig-like domains The role of highly conserved proline residues in the fibronectin type III superfamily. J. Mol. Biol. 2002, 318, 935-40. 

IL-IOR is a single-chain receptor. IL-IOR belongs to the class II cytokine receptor family that also includes the IFN receptors (IFNy and IFNap receptors). The extracellular region consists of two homologous fibronectin type III domains that are without the WSXWS motif characteristic of class I cytokine receptors. It is expressed on B cells, thymocytes, and other cellular lines such as mast cells and macrophages. Human IL-IOR mRNA is restricted mostly to hematopoietic cells and cell lines. ... 

FG-Loop (FGL), a neural cell adhesion molecule-derived peptide that corresponds to its second fibronectin type III module, has been shown to provide neuroprotection against a range of cellular insults. FGL improves memory and alleviates the deleterious effects on CA1 pyramidal cells induced by AP25-35 injection. These effects might be due to inactivation of GSK3P [597]. 

The Ig-superfamily contains many proteins involved in immune recognition such as products of the MHC complex and accessory molecules [53]. In addition there are ten or more members associated mainly with nervous tissues in mature animals and several others in non-nervous tissue that are important factors in cell-cell and cell-substratum adhesion in non-immune cells. See [54] and [55] for detailed discussion of other aspects of Ig-superfamily glycoproteins. All of the cell adhesion glycoproteins in the family contain a variable number of Ig-like domains of about one hundred amino-acid residues, usually but not always defined within a pair of disulfide-bonded cysteine residues, and of the C2 type fold. In many cases the molecules contain variable numbers of another type of modular sequence known as the fibronectin type III repeat, sinee it was discovered in fibroneetin. In the following discussion, some principles of the structure and functions of this large family of cell adhesion molecules will be considered with particular emphasis on the interplay between different members in adhesion and modulation of adhesive interactions by carbohydrates. 

Fig. 8. Structures of LI, MAG and PO glycoproteins. The sequences of LI (a), MAG (b) and PO (c) glycoproteins predicted from analysis of cDNA clones as well as protein in the case of PO are shown to variably include in the extracellular portions Ig-like domains, fibronectin type III repeats (hatched), a transmembrane segment and a cytoplasmic domain. Potential A-glycosylation sites are indicated (open circle). Splicing variants in the cytoplasmic domains of LI and MAG are shown (open triangle).

---