Structure of Transferrins

The bilobal structure of transferrins means that half-molecules, representing either the N-terminal or C-terminal lobe, can be relatively easily prepared, either by limited proteolysis or by recombinant DNA methods (Section III.A). Relatively high-resolution crystal structures have been determined for three such half-molecules, the proteolytic N-lobes of rabbit transferrin (74) and chicken ovotransferrin (77) at 2.3 A and the recombinant N-lobe of human lactoferrin at 2.0-A resolution (75). These show that both the protein structure and the metal and anion binding sites are the same as in the intact parent structures. In fact comparison of the metal and anion sites of the lactoferrin and transferrin half-molecules with each other and with the N-lobe of lactoferrin shows very close correspondence 92 atoms from the nine residues, plus metal and anion, making up the immediate binding site can be superimposed with an rms deviation of only 0.4 A (75). 

Figure 5.7 Structures of the alternative conformations of the iron-binding sites in the orthorhombic crystal form of the recombinant N-lobe of human transferrin. Reproduced with permission from MacGillivray et ah, 1998. Copyright (1998), American Chemical Society. 

The determination of the structure of the iron transporter, ferric-binding, protein (hFBP)t from Haemophilus influenzae (Bruns et ah, 1997) at 0.16 nm resolution shows that it is a member of the transferrin superfamily, which includes both the transferrins and a number of periplasmic binding proteins (PBP). The PBPs transport a wide variety of nutrients, including sugars, amino acids and ions, across the periplasm from the outer to the inner (plasma) membrane in bacteria (see Chapter 3). Iron binding by transferrins (see below) requires concomitant binding of a carbonate anion, which is located at the N-terminus of a helix. This corresponds to the site at which the anions are specifically bound in the bacterial periplasmic sulfate- and... 

A recently obtained high resolution structure of two crystal forms of the N-lobe of human serum transferrin (at 0.16 and 0.18 nm resolution) shows disorder at the iron-binding sites (MacGillivray et ah, 1998). Model building and refinement show... 

Figure 7.4 (a) IREs in eukaryotic mRNAs the secondary structures of ferritin and transferrin receptor IREs. (b) The IRE localization in mRNAs the translation/ribosome binding element in the 5 -UTR of ferritin mRNA is above, that of the stability/ turnover element in the 3 -UTR of transferrin receptor mRNA is below. Adapted from Theil, 1998, by courtesy of Marcel Dekker, Inc. 

Smith, C.A., Anderson, B.F., Baker, H.M., and Baker, E.N. 1992. Metal substitution in transferrins the crystal structure of human copper-lactoferrin at 2.1-A resolution. Biochemistry 31 4527 -533. 

MacGillivray, R.T., Moore, S.A., Chen, J., Anderson, B.F., Baker, H., Luo, Y., Bewley, M., Smith, C.A., Murphy, M.E., Wang, Y., Mason, A.B., Woodworth, R.C., Brayer, G.D. and Baker, E.N. (1998) Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release, Biochemistry, 37, 7919-7928. 

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