Author ORCID Identifier
Document Type
Article
Publication Date
12-1-2005
Abstract
The structural allostery and binding interface for the human serum transferrin (Tf)-transferrin receptor (TfR) complex were identified using radiolytic footprinting and mass spectrometry. We have determined previously that the transferrin C-lobe binds to the receptor helical domain. In this study we examined the binding interactions of full-length transferrin with receptor and compared these data with a model of the complex derived from cryoelectron microscopy (cryo-EM) reconstructions (Cheng, Y., Zak, O., Aisen, P., Harrison, S. C. & Walz, T. (2004) Structure of the human transferrin receptor-transferrin complex. Cell 116, 565-576). The footprinting results provide the following novel conclusions. First, we report characteristic oxidations of acidic residues in the C-lobe of native Tf and basic residues in the helical domain of TfR that were suppressed as a function of complex formation; this confirms ionic interactions between these protein segments as predicted by cryo-EM data and demonstrates a novel method for detecting ion pair interactions in the formation of macromolecular complexes. Second, the specific side-chain interactions between the C-lobe and N-lobe of transferrin and the corresponding interactions sites on the transferrin receptor predicted from cryo-EM were confirmed in solution. Last, the footprinting data revealed allosteric movements of the iron binding C- and N-lobes of Tf that sequester iron as a function of complex formation; these structural changes promote tighter binding of the metal ion and facilitate efficient ion transport during endocytosis.
Publication Title
Molecular & Cellular Proteomics
Volume
4
Issue
12
First Page
1959
Last Page
1967
Rights
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Guozhong Xu, Rutao Liu, Olga Zak, Philip Aisen, Mark R. Chance. Structural Allostery and Binding of the Transferrin·Receptor Complex. Molecular & Cellular Proteomics, Volume 4, Issue 12, 2005, Pages 1959-1967, https://doi.org/10.1074/mcp.M500095-MCP200.