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Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy
Published on: August 15, 2014
Structure and dynamics of human apolipoprotein CIII
Chinthaka Saneth Gangabadage1, Janusz Zdunek, Marco Tessari
1Department of Physical Chemistry-Biophysical Chemistry, Radboud University of Nijmegen, Toernooiveld 1, 6525 ED, Nijmegen, The Netherlands.
The Journal of Biological Chemistry
|April 15, 2008
Summary
Human apolipoprotein CIII (apoCIII), a protein linked to high blood lipids, was studied in its lipid-bound state. Its structure reveals how apoCIII inhibits enzymes and receptor binding, offering insights into hypertriglyceridemia.
Area of Science:
- Biochemistry
- Structural Biology
- Lipid Metabolism
Background:
- Human apolipoprotein CIII (apoCIII) is a key lipoprotein component.
- Elevated apoCIII levels correlate with hypertriglyceridemia.
- ApoCIII inhibits lipoprotein lipase and receptor binding.
Purpose of the Study:
- Determine the 3D NMR structure and dynamics of human apoCIII in a lipid-bound state.
- Understand the molecular mechanisms of apoCIII's inhibitory functions.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy.
- Residual dipolar coupling analysis.
- SDS micelle complex formation to mimic lipid-bound state.
Main Results:
- Detailed 3D structure and dynamics of intact apoCIII on SDS micelles obtained.
- ApoCIII adopts a 'necklace' conformation of six amphipathic helices.
- Asymmetric charge distribution on apoCIII's surface identified, conserved across mammals.
Conclusions:
- The determined structure provides a molecular template for apoCIII function.
- Insights into apoCIII's inhibition of lipoprotein lipase and receptor interactions.
- Structural conservation suggests a fundamental role in lipid metabolism.
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