Abstract
PROTEINS of the transferrin family, which contains serum transferri n and lactoferrin, control iron levels in higher animals through their very tight (Kapp ~1020) but reversible binding of iron1,2. These bilobate molecules3,4 have two binding sites, one per lobe, each housing one Fe3+ and the synergistic CO323– ion5. Crystallographic studies of human lactoferrin4,6 and rabbit serum transferrin7 in their iron-bound forms have characterized their binding sites and protein structure. Physical studies8,9 show that a substantial conformational change accompanies iron binding and release. We have addressed this phenomenon through crystal structure analysis of human apolactoferrin at 2.8 Å resolution. In this structure the N-lobe binding cleft is wide open, following a domain rotation of 53°, mediated by the pivoting of two helices and flexing of two interdomain polypeptide strands. Remarkably, the C-lobe cleft is closed, but unliganded. These observations have implications for transferrin function and for binding proteins in general.
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Andersen, B., Baker, H., Morris, G. et al. Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. Nature 344, 784–787 (1990). https://doi.org/10.1038/344784a0
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DOI: https://doi.org/10.1038/344784a0
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