HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M500095-MCP200v1 4/12/1959    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Glossary Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xu, G. Articles by Chance, M. R. Search for Related Content PubMed PubMed Citation Articles by Xu, G. Articles by Chance, M. R. Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 4:1959-1967, 2005.
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Research

Structural Allostery and Binding of the Transferrin·Receptor Complex^*,S

Guozhong Xu^,, Rutao Liu^,¶, Olga Zak^¶, Philip Aisen^¶ and Mark R. Chance^,||

From the Case Center for Proteomics and Mass Spectrometry, Case Western Reserve University, Cleveland, Ohio 44106 and the ^¶ Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. K. A. Kamal, S. A. Benchaar, K. Takamoto, E. Reisler, and M. R. Chance Three-dimensional structure of cofilin bound to monomeric actin derived by structural mass spectrometry data PNAS, May 8, 2007; 104(19): 7910 - 7915. [Abstract] [Full Text] [PDF]

				J. G. Kiselar, R. Mahaffy, T. D. Pollard, S. C. Almo, and M. R. Chance Visualizing Arp2/3 complex activation mediated by binding of ATP and WASp using structural mass spectrometry PNAS, January 30, 2007; 104(5): 1552 - 1557. [Abstract] [Full Text] [PDF]

				J. Wally, P. J. Halbrooks, C. Vonrhein, M. A. Rould, S. J. Everse, A. B. Mason, and S. K. Buchanan The Crystal Structure of Iron-free Human Serum Transferrin Provides Insight into Inter-lobe Communication and Receptor Binding J. Biol. Chem., August 25, 2006; 281(34): 24934 - 24944. [Abstract] [Full Text] [PDF]

				E. Wang, L. Albritton, and S. R. Ross Identification of the Segments of the Mouse Transferrin Receptor 1 Required for Mouse Mammary Tumor Virus Infection J. Biol. Chem., April 14, 2006; 281(15): 10243 - 10249. [Abstract] [Full Text] [PDF]