Serum transferrins half-molecules

Ser Se isotopic substitution, 38 105-107 Serum albumin, 46 470 Serum transferrins, 41 390 biological role, 41 391-392 half-molecules, 41 396 recombinant, 41 453 structure, 41 397... 

Complementing the structural studies of the intact transferrins, a number of fragments have also been crystallized, including proteolytic N-terminal half-molecules of rabbit serum transferrin (69) and chicken ovotransferrin (70), recombinant N-terminal half-molecules of human lactoferrin (71) and human serum transferrin (72), and a quarter-molecule fragment of duck ovotransferrin (73). All of these have now led to high-resolution structures (74-77). 

Where chemical or physical differences can be detected between the two sites, there remains the problem of distinguishing which site is which. For serum transferrin this is helped immensely by the ability to prepare monoferric forms, loaded in either the N- or C-site (198, 200), and to be able to separate them by electrophoresis in 6 Ilf urea, the Makey-Seal method (201). This enabled the so-called A and B sites, differentiated in earlier studies, to be identified with the C- and N-terminal sites, respectively (202). Comparisons of the diferric proteins with N- and C-loaded monoferric transferrins or (more recently) recombinant half-molecules have by now revealed a number of inequivalences. 

Fig. 28. The pH dependence of iron release from human serum transferrin (Tf), human lactoferrin (Lf), and the recombinant N-terminal half-molecule of human lactoferrin (Lfm). Also shown is a plot (dashed line) for the release of cerium from Ce4+-substituted lactoferrin, demonstrating the increased difference between the two sites for metal ions other than Fe3+.

Under normal physiological conditions, iron is transported in serum by transferrin, an 80 kDa bilobal protein with two almost identical iron-binding sites, one in each half of the molecule. 

Most mammalian cells take up iron transported in serum by transferrin, an 80 kD bilobal protein with two identical iron-binding sites, one in each half of the molecule. The coordination of the iron atom involves four protein ligands and a carbonate anion, as we described in Chapter 4, and the transferrin to cell cycle for delivering iron was outlined in Chapter 7. Iron release from the extremely stable diferric transferrrin bound to its receptor is facilitated by the acidic pH prevailing in the endosome and by the fact that the receptor imposes a conformation on the bound transferrin that is essentially that of the open apotransferrin form. 

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