title: Single particle reconstruction of the human apo-transferrin-transferrin receptor complex.
abstract: 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 (Fe3+) form and potentially toxic in its ferrous (Fe2+) 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 16A, 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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. ycheng@hms.harvard.edu
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Olga
authors.initials: O
authors.lastname: Zak
authors.forename: Philip
authors.initials: P
authors.lastname: Aisen
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
mesh_terms: D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D001059:Apoproteins; D010446:Peptide Fragments; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D014168:Transferrin; C028284:apotransferrin; C028283:diferric transferrin