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Crystal structures of saposins A and C
Victoria E Ahn1, Paul Leyko, Jean-René Alattia
1Department of Medical Biophysics, University of Toronto, Canada.
Protein Science : a Publication of the Protein Society
|July 11, 2006
Summary
Saposins A and C are crucial for breaking down specific lipids in lysosomes. Their structures reveal a compact fold, but they self-assemble into dimers or trimers at acidic pH, impacting their function.
Area of Science:
- Biochemistry
- Structural Biology
- Lysosomal Storage Diseases
Background:
- Saposins A and C are essential sphingolipid activator proteins.
- They facilitate the lysosomal hydrolysis of specific lipids like galactosylceramide and glucosylceramide.
- Saposins enhance lipid accessibility to hydrolases.
Purpose of the Study:
- To determine the crystal structures of human saposins A and C.
- To investigate the oligomeric state of saposins A, B, and C in solution under varying pH and detergent conditions.
- To understand the structural basis of saposin function and self-association.
Main Methods:
- X-ray crystallography to determine protein structures.
- Analytical ultracentrifugation to assess protein oligomerization in solution.
- Experiments conducted at different pH values (7.0 and 4.8) and in the presence of detergent C(8)E(5).
Main Results:
- Crystal structures of human saposins A and C revealed a compact, monomeric fold.
- At pH 7.0, saposins A and C were confirmed to be monomeric in solution.
- At pH 4.8 with detergent, saposin A formed dimers, saposin C formed trimers, and saposin B was consistently dimeric.
Conclusions:
- The determined crystal structures provide insights into the fundamental saposin fold.
- Saposin self-assembly into different oligomeric states is pH-dependent and may be crucial for their interaction with lipids and enzymes.
- These findings are relevant to understanding the mechanisms underlying lysosomal lipid metabolism and related disorders.
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