Document Detail


The molecular mechanism for receptor-stimulated iron release from the plasma iron transport protein transferrin.
MedLine Citation:
PMID:  16271884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human transferrin receptor 1 (TfR) binds iron-loaded transferrin (Fe-Tf) and transports it to acidic endosomes where iron is released in a TfR-facilitated process. Consistent with our hypothesis that TfR binding stimulates iron release from Fe-Tf at acidic pH by stabilizing the apo-Tf conformation, a TfR mutant (W641A/F760A-TfR) that binds Fe-Tf, but not apo-Tf, cannot stimulate iron release from Fe-Tf, and less iron is released from Fe-Tf inside cells expressing W641A/F760A-TfR than cells expressing wild-type TfR (wtTfR). Electron paramagnetic resonance spectroscopy shows that binding at acidic pH to wtTfR, but not W641A/F760A-TfR, changes the Tf iron binding site > or =30 A from the TfR W641/F760 patch. Mutation of Tf histidine residues predicted to interact with the W641/F760 patch eliminates TfR-dependent acceleration of iron release. Identification of TfR and Tf residues critical for TfR-facilitated iron release, yet distant from a Tf iron binding site, demonstrates that TfR transmits long-range conformational changes and stabilizes the conformation of apo-Tf to accelerate iron release from Fe-Tf.
Authors:
Anthony M Giannetti; Peter J Halbrooks; Anne B Mason; Todd M Vogt; Caroline A Enns; Pamela J Björkman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Structure (London, England : 1993)     Volume:  13     ISSN:  0969-2126     ISO Abbreviation:  Structure     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-07     Completed Date:  2008-07-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101087697     Medline TA:  Structure     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1613-23     Citation Subset:  IM    
Affiliation:
Division of Biology 114-96, California Institute of Technology, Pasadena, California 91125, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / genetics,  metabolism*
Binding Sites
Electron Spin Resonance Spectroscopy
Histidine / metabolism
Humans
Iron / blood*,  metabolism
Mutation
Phenylalanine / metabolism
Protein Transport
Receptors, Transferrin / genetics,  metabolism*
Transferrin / metabolism*
Tryptophan / metabolism
Grant Support
ID/Acronym/Agency:
5T32-GM-7616/GM/NIGMS NIH HHS; R01 DK21739/DK/NIDDK NIH HHS; R01 DK54488/DK/NIDDK NIH HHS; R01 DK60770/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/CD71 antigen; 0/Receptors, Transferrin; 11096-37-0/Transferrin; 63-91-2/Phenylalanine; 71-00-1/Histidine; 73-22-3/Tryptophan; 7439-89-6/Iron

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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