Polypeptide chain, transferrins

Polyoxygen fluoride radicals, 16 115 Polypeptide chain, transferrins, 41 397-398 folding, 41 400-402, 417-418 Polypeptide folding, iron-sulfur proteins, 47 271-276... 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

Figure 9.11 Structure of an oligosaccharide unit of human transferrin. The linkage between the oligosaccharide and polypeptide chains is of the N-asparaginyl type. Dotted arrows indicate positions in which one sometimes finds NeuNAc-Gal-GlcNAc units. Gal is galactose, GIcNAc is N-acetylglucosamine, NeuNAc is N-acetylneuraminic acid (sialic acid), and Man is mannose. (Reproduced with permission from Bezkorovainy A. Biochemistry of Nonheme Iron. New York Plenum Press, 1980, p. 175.)...

The transferrins are typically monomeric glycoproteins with a single polypeptide chain of 670-700 amino acids and a molecular weight of —80,000. Their characteristic property is to bind, very tightly but reversibly, two Fe3+ ions together with two CO ions. The relationship... 

All transferrins characterized so far consist of a single polypeptide chain of 670-700 amino acid residues. The lactoferrin and serum transferrin structure analyses show that the folding (polypeptide chain conformation) is the same in both proteins and, given their sequence homology, can be assumed to hold for all proteins of the transferrin family. 

The polypeptide chain is first of all folded into two globular lobes, representing the N-terminal and C-terminal halves of the molecule these are referred to as the N-lobe and C-lobe, respectively. In human lactoferrin the N-lobe comprises residues 1-333 and the C-lobe, residues 345-691, whereas in rabbit serum transferrin the equivalent lobes comprise 1-328 and 342-676. Each lobe contains a single iron binding site, and each has essentially the same folding (described more fully in Section III.B.2). The two lobes do not have equivalent orientations... 

Lactoferrin has been isolated and identified from a wide variety of animal species. However, most of the studies on structure and iron-binding properties have involved either human or bovine proteins (2). Lactoferrin closely resembles transferrin in molecular weight of 75,000 to 90,000 and consists of a single polypeptide chain that binds two ferric ions. The pi of transferrin is 5.9 while that of lactoferrin is approximately 9.0 (8) and has an even higher association constant for iron-binding. Lactoferrin has the property of retaining its iron even in the presence of a relatively low-affir-nity iron chelator such as citrate below pH 4.0. Transferrin, on the other hand, looses its iron when the pH is lowered from 6 to 5 (7). There is extensive information in the literature concerning the physical properties of lactoferrin which will not be covered in this paper. 

The transferrins are glycoproteins (i.e. compounds of proteins and carbohydrates) and include serum transferrin, lactoferrin (present in milk) and ovotransferrin (present in egg white). In humans, serum transferrin transports 40 mg of iron per day to the bone marrow. It contains a single polypeptide chain (molecular weight of 80000) coiled in such a way as... 

The general properties of this protein are summarized in Table 2. Four copper atoms are bound per molecular weight 62—64,000, and the work of Butzow (53) suggests that if the enzyme is polymeric it does not consist of subunits which are easily dissociated. Indeed it appears that this protein, like transferrin, (MW 80,000), may consist of only one polypeptide chain [cf. (54)). 

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