Related Experiment Videos
Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins
B F Anderson1, H M Baker, G E Norris
1Department of Chemistry and Biochemistry, Massey University, Palmerston North, New Zealand.
Nature
|April 19, 1990
Summary
Transferrin proteins tightly bind iron. Structural analysis of human apolactoferrin reveals open and closed binding sites, explaining iron binding and release mechanisms in these vital proteins.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Transferrin family proteins, including serum transferrin and lactoferrin, regulate iron homeostasis in animals.
- These proteins exhibit high-affinity, reversible iron binding via two bilobate binding sites.
- Iron binding and release are associated with significant conformational changes.
Purpose of the Study:
- To investigate the structural basis of conformational changes in transferrin proteins during iron binding and release.
- To analyze the crystal structure of human apolactoferrin (iron-free form) to understand its conformational state.
Main Methods:
- X-ray crystallography was employed to determine the structure of human apolactoferrin at 2.8 Å resolution.
- Comparative analysis with iron-bound transferrin structures was performed.
Main Results:
- The N-lobe binding cleft of human apolactoferrin was observed to be open, with a 53-degree domain rotation.
- The C-lobe binding cleft was found to be closed, despite being unliganded.
- Specific structural elements, including helix pivoting and strand flexing, mediate the observed domain movement.
Conclusions:
- The open N-lobe and closed C-lobe in apolactoferrin provide structural insights into the mechanism of iron binding and release.
- These findings have implications for understanding the function of transferrins and other ligand-binding proteins.