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Structural allostery and binding of the transferrin*receptor complex.
Guozhong Xu1, Rutao Liu, Olga Zak
1Case Center for Proteomics and Mass Spectrometry, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Molecular & Cellular Proteomics : MCP
|December 8, 2005
Summary
Structural allostery and binding interfaces of the human transferrin (Tf) and transferrin receptor (TfR) complex were identified. This study confirms ionic interactions and reveals allosteric movements that enhance iron binding and transport during endocytosis.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Interactions
Background:
- The human serum transferrin (Tf) and transferrin receptor (TfR) complex is crucial for iron uptake.
- Previous studies identified that the Tf C-lobe binds to the TfR helical domain.
Purpose of the Study:
- To identify the structural allostery and binding interface of the human Tf-TfR complex.
- To compare experimental data with existing cryo-electron microscopy (cryo-EM) models.
Main Methods:
- Radiolytic footprinting
- Mass spectrometry
- Comparison with cryo-EM data
Main Results:
- Confirmed ionic interactions between acidic residues in Tf C-lobe and basic residues in TfR helical domain.
- Validated side-chain interactions between Tf lobes and TfR binding sites in solution.
- Revealed allosteric movements in Tf lobes upon complex formation, sequestering iron.
Conclusions:
- Radiolytic footprinting provides a novel method for detecting ion pair interactions in macromolecular complexes.
- Structural changes in Tf promote tighter iron binding and facilitate efficient ion transport.
- The study elucidates key molecular mechanisms of iron transport via the Tf-TfR pathway.