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How α-Helical Motifs Form Functionally Diverse Lipid-Binding Compartments.
Lucy Malinina1, Dinshaw J Patel2, Rhoderick E Brown1
1The Hormel Institute, University of Minnesota, Austin, Minnesota 55912; email: lucy@hi.umn.edu , reb@umn.edu.
Annual Review of Biochemistry
|April 5, 2017
Summary
Alpha-helical proteins utilize layered and bundled structures to bind lipids for transport. The glycolipid transfer protein (GLTP) fold offers a simple, elegant model for understanding these lipid-binding compartments.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Lipids are synthesized in specific cellular locations and distributed non-uniformly across membranes.
- Non-vesicular lipid transport relies on soluble amphitropic proteins acting as molecular solubilizers.
- Lipid-binding proteins exhibit diverse structural motifs, including barrels, cups, baskets, and helical bundles.
Purpose of the Study:
- To investigate how alpha-helical proteins form modular lipid-binding compartments through amphipathic helical layering and bundling.
- To discuss the functional implications of these alpha-helical lipid-binding structures.
- To advance the understanding of lipid transport mechanisms by focusing on the glycolipid transfer protein (GLTP) fold.
Main Methods:
- Focus on structural analysis of alpha-helical proteins involved in lipid binding and transfer.
- Examination of preformed lipid-binding compartments stabilized by disulfide bridges.
- Analysis of nonpreformed hydrophobic compartments, drawing parallels with nuclear receptor ligand-binding domains.
- Detailed study of the two-layer, alpha-helical glycolipid transfer protein (GLTP) fold.
Main Results:
- Alpha-helical proteins employ amphipathic helical layering and bundling to create modular lipid-binding compartments.
- Preformed compartments often rely on intramolecular disulfide bonds for structural integrity.
- Nonpreformed compartments, which adapt to lipid cargo, are less understood but exemplified by nuclear receptors.
- The GLTP fold provides a fundamental and widely applicable model for alpha-helical lipid-binding structures.
Conclusions:
- Alpha-helical protein structures are crucial for the formation of functional lipid-binding compartments.
- The GLTP fold represents a key structural motif that advances our understanding of lipid transport.
- Further research into nonpreformed compartments is needed to fully elucidate lipid trafficking mechanisms.