Transferrins conformation changes

In Figure 2.12(b) is shown the temperature dependence of the rate constant for iron removal from N-terminal monoferric transferrin. There is an obvious break between 12 and 20 °C and this is ascribed to a temperature-induced conformational change. The effect becomes less distinct when the ionic strength is increased from 0.13 to 2.0 M,See also Sec. 4.11. 

On release of iron, transferrin undergoes a major conformational change, characterized by a hydrodynamically less compact structure. Crystallographic analysis of apolactoferrin reveals that the amino-... 

Transferrins bind Fe2+ weakly and it is likely that a transferrin- Fe2+-HC03- complex formed initially undergoes oxidation to the Fe3+-C032- complex within cells and within the bloodstream. A conformational change closes the protein around the iron ions.56 In yeast the previously mentioned copper oxidoreductase encoded by the FET3 gene appears to not only oxidize Fe2+ but also transfer the resulting Fe3+ to transferrin. Ceruloplasmin may play a similar role in mammals.33... 

Solution scattering measurements on half-molecules show that they undergo very similar conformational changes, on iron binding or release, to those of the corresponding lobes of intact transferrins (104). This, together with the structural correspondence noted above, makes them valid as models of single-sited transferrins. The lactoferrin half-... 

Another variation that may affect the dynamic properties of different transferrins is in the number and distribution of disulfide bonds. Because conformational change is important for metal binding and release (Section V) the restraints imposed by these covalent bridges may be important. The likely distribution of disulfide bonds in different species is given in Table V. While these are deduced from sequence alignments and are thus tentative, several conclusions can be drawn. All species appear to have the same six conserved disulfide bonds in their N-lobe... 

Conformational change to the final specific transferrin complex. 

Most kinetic studies of iron release have focused on pathways involving the use of chelate ligands such as EDTA (217), pyrophosphate 218-220), phosphonates 220,221), catecholates 108,216), hydroxa-mates 120), and nitrilotriacetate (221). In many cases, simple saturation kinetics are observed, and interpreted in terms of the formation of a quaternary complex, ligand-Fe-transferrin-COs (120,122). The failure to observe this complex spectroscopically [in contrast to iron uptake studies (120)] has been explained in terms of a rate-limiting conformational change, giving a basic three-step mechanism, which is essentially the reverse of that given for iron uptake (Section V.A.l). 

Anderson, B. F., Baker, H. M., Norris, G. E., Rumball, S. V. Baker, E. N. (1990). Apolactoferrin structure demonstrates ligand-induced conformational changes in transferrins. Nature (London), 344,784-7. 

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