Related Experiment Videos
Solution structure of human saposin C: pH-dependent interaction with phospholipid vesicles
Eva de Alba1, Solly Weiler, Nico Tjandra
1Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 Center Drive, Bethesda, Maryland 20892, USA. dealba@helix.nih.gov
Biochemistry
|December 17, 2003
Summary
Saposin C protein binds to membranes, activating lipid breakdown in lysosomes. Its function is regulated by pH-dependent membrane neutralization, suggesting a switch for lysosomal lipid degradation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Saposin C is a lysosomal protein crucial for lipid degradation.
- Understanding its membrane interaction mechanism is key to lysosomal function.
Purpose of the Study:
- To elucidate the three-dimensional structure of Saposin C.
- To investigate Saposin C's interaction with phospholipid vesicles.
- To understand the role of pH in Saposin C's membrane binding and function.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to determine protein structure.
- Investigation of Saposin C's binding to phospholipid vesicles.
- Analysis of mutant Saposin C with altered surface charge.
Main Results:
- Saposin C adopts a common saposin fold but possesses a unique electrostatic surface.
- Membrane binding is a pH-controlled reversible process with a pK(a) near 5.3.
- Partial neutralization of Saposin C's negative surface charge is required for membrane binding.
Conclusions:
- Protein surface charge distribution influences membrane interaction and functional diversity.
- Saposin C's reversible, pH-dependent membrane binding suggests a mechanism to regulate lysosomal lipid degradation.
- This provides insights into controlling lipid breakdown within lysosomes.