On allosteric modulation of P-type Cu(+)-ATPases
Daniel Mattle1, Oleg Sitsel, Henriette E Autzen
1Centre for Membrane Pumps in Cells and Disease (PUMPkin), Danish National Research Foundation, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
Journal of Molecular Biology
|March 19, 2013
Summary
P-type ATPases transport compounds across membranes. This study compares copper-transporting ATPases (PIB) to calcium-transporting ATPases (PIIA), revealing subclass-specific features that modulate ion transport mechanisms.
Area of Science:
- Biochemistry
- Molecular Biology
- Membrane Transport
Background:
- P-type ATPases are essential membrane proteins for active transport and cellular homeostasis.
- They share a common functional cycle involving phosphoenzyme intermediates but exhibit subclass-specific adaptations.
- Copper-transporting ATPases (subclass PIB) and sarco(endo)plasmic reticulum Ca(2+)-ATPase (subclass PIIA) represent distinct functional classes.
Purpose of the Study:
- To provide an overview of Cu(+)-transporting ATPases (subclass PIB).
- To compare Cu(+)-ATPases with the well-characterized Ca(2+)-ATPase (subclass PIIA).
- To investigate the structural and mechanistic differences influencing transport specificity.
Main Methods:
- Comparative analysis of P-type ATPase subclasses.
- Database analysis of copper-ligating residues.
- Review of structural and sequence motifs related to transport function.
Main Results:
- Cu(+)-ATPases interact with soluble chaperones via an intracellular docking platform.
- Heavy-metal binding domains suggest allosteric regulation of Cu(+)-ATPase activity.
- Database analysis challenges the two-site model for intramembranous copper binding, proposing a role in translocation and proton exchange.
Conclusions:
- Subclass-specific features in P-type ATPases allow for tailored energy coupling mechanisms.
- Topological diversity enables adaptation for transporting diverse compounds with distinct properties.
- Understanding these differences is key to elucidating specific ion homeostasis and transport functions.
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