title: Structural and functional studies on the stalk of the transferrin receptor.
abstract: Transferrin (Tf) is an iron carrier protein that consists of two lobes, the N- and C-lobes, which can each bind a Fe(3+) ion. Tf binds to its receptor (TfR), which mediates iron delivery to cells through an endocytotic pathway. Receptor binding facilitates iron release from the Tf C-lobe, but impedes iron release from the N-lobe. An atomic model of the Tf-TfR complex based on single particle electron microscopy (EM) indicated that receptor binding is indeed likely to hinder opening of the N-lobe, thus interfering with its iron release. The atomic model also suggested that the TfR stalks could form additional contacts with the Tf N-lobes, thus potentially further slowing down its iron release. Here, we show that the TfR stalks are unlikely to make strong interactions with the Tf N-lobes and that the stalks have no effect on iron release from the N-lobes of receptor-bound Tf.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Danijela
authors.initials: D
authors.lastname: Dukovski
authors.forename: Zongli
authors.initials: Z
authors.lastname: Li
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Kelly
authors.forename: Eric
authors.initials: E
authors.lastname: Mack
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
mesh_terms: D020285:Cryoelectron Microscopy; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011990:Receptors, Transferrin / Q000737:chemistry* / Q000378:metabolism*; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron