| Structural allostery and binding of the transferrin*receptor complex. | |
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MedLine Citation:
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PMID: 16332734 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Guozhong Xu; Rutao Liu; Olga Zak; Philip Aisen; Mark R Chance |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2005-09-16 |
Journal Detail:
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Title: Molecular & cellular proteomics : MCP Volume: 4 ISSN: 1535-9476 ISO Abbreviation: Mol. Cell Proteomics Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-12-07 Completed Date: 2006-03-28 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 101125647 Medline TA: Mol Cell Proteomics Country: United States |
Other Details:
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Languages: eng Pagination: 1959-67 Citation Subset: IM |
Affiliation:
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Case Center for Proteomics and Mass Spectrometry, Case Western Reserve University, Cleveland, Ohio 44106, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allosteric Regulation Amino Acid Sequence Binding Sites Cryoelectron Microscopy Humans Iron / metabolism Mass Spectrometry Models, Molecular Molecular Sequence Data Protein Conformation Receptors, Transferrin / chemistry*, metabolism*, ultrastructure |
| Grant Support | |
ID/Acronym/Agency:
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P41-EB-01979/EB/NIBIB NIH HHS; R21-DK-69952/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Transferrin; 7439-89-6/Iron |
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