Single particle reconstruction of the human apo-transferrin–transferrin receptor complex

• Published in: Journal of structural biology Vol. 152; no. 3; pp. 204 - 210
• Main Authors: Cheng, Yifan, Zak, Olga, Aisen, Philip, Harrison, Stephen C., Walz, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2005
• Subjects: Apo-transferrin; Apoproteins - chemistry; Apoproteins - metabolism; Apoproteins - ultrastructure; Cryoelectron Microscopy; Humans; Imaging, Three-Dimensional; Models, Molecular; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - ultrastructure; Protein Binding; Receptors, Transferrin - chemistry; Receptors, Transferrin - metabolism; Receptors, Transferrin - ultrastructure; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Recombinant Proteins - ultrastructure; Single particle electron microscopy; Transferrin - chemistry; Transferrin - metabolism; Transferrin - ultrastructure; Transferrin receptor; Single particle electron microscopy; Transferrin receptor; Apo-transferrin
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2005.10.006

Most organisms depend on iron as a co-factor for proteins catalyzing redox reactions. Iron is, however, a difficult element for cells to deal with, as it is insoluble in its ferric (Fe 3+) form and potentially toxic in its ferrous (Fe 2+) form. Thus, in vertebrates iron is transported through the circulation bound to transferrin (Tf) and delivered to cells through an endocytotic cycle involving the transferrin receptor (TfR). We have previously presented a model for the Tf–TfR complex in its iron-bearing form, the diferric transferrin (dTf)–TfR complex [Cheng, Y., Zak, O., Aisen, P., Harrison, S.C., Walz, T., 2004. Structure of the human transferrin receptor–transferrin complex. Cell 116, 565–576]. We have now calculated a single particle reconstruction for the complex in its iron-free form, the apo-transferrin (apoTf)–TfR complex. The same density map was obtained by aligning raw particle images or class averages of the vitrified apoTf–TfR complex to reference models derived from the structures of the dTf–TfR or apoTf–TfR complex. We were unable to improve the resolution of the apoTf–TfR density map beyond 16 Å, most likely because of significant structural variability of Tf in its iron-free state. The density map does, however, support the model for the apoTf–TfR we previously proposed based on the dTf–TfR complex structure, and it suggests that receptor-bound apoTf prefers to adopt an open conformation.