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Computational structure models of apo and diferric transferrin-transferrin receptor complexes
Tetsuya Sakajiri1, Takaki Yamamura, Takeshi Kikuchi
1Department of Applied Chemistry, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601, Japan.
The Protein Journal
|October 20, 2009
Summary
Structural models reveal how transferrin (Tf) binds its receptor (TfR) for iron uptake. A key TfR residue, R651, interacts with Tf E385, explaining Tf-TfR complex dynamics and iron release.
Area of Science:
- Biochemistry
- Structural Biology
- Cell Biology
Background:
- Transferrin (Tf) and its receptor (TfR) mediate cellular iron uptake.
- Previous studies utilized mutagenesis to understand Tf-TfR complexation.
Purpose of the Study:
- To create 3D structural models of apo-human Tf-TfR and Fe(III)2Tf-TfR complexes.
- To interpret Tf-TfR complexation and iron release mechanisms.
Main Methods:
- Computational rigid body refinement was used to generate 3D structural models.
- Models were validated against published mutagenesis data.
Main Results:
- Models show C-lobes of Tf binding the TfR helical domain; N-lobes are positioned between the TfR ectodomain and cell membrane.
- No significant conformational changes in Tf were observed upon complexation.
- Identified a novel interaction between TfR residue R651 (a binding hot spot) and Tf residue E385 in both apoTf-TfR and Fe(2)Tf-TfR complexes.
Conclusions:
- The models provide a structural basis for Tf-TfR interactions.
- The findings explain iron release from Fe(2)Tf-TfR at low pH and apoTf dissociation at alkaline pH.
- The study elucidates metal-specific recognition by TfR.
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