Does alpha-helix folding necessarily provide an energy source for the protein-lipid binding?
Lipid-induced alpha-helix folding, which occurs in many lipid surface-binding proteins and peptides such as apolipoproteins and synucleins, has been proposed to provide an energy source for protein-lipid interactions. We propose that in a system comprised of a phospholipid surface and a small polypeptide that is unfolded in solution and binds reversibly to lipid surface, helical folding involves expenditure of free energy as compared to a similar polypeptide that is alpha-helical in solution. This is a consequence of the entropic cost of helix folding that is illustrated in a simple thermodynamic model and exemplifies the general "key-into-lock" paradigm of protein-ligand binding. Even though this simple model does not explicitly address the protein-induced lipid re-arrangement and may not directly apply to large proteins that undergo significant tertiary structural changes upon lipid binding, it suggests that the notion of helix folding as an energy source for lipid binding should be treated with caution.
Gursky
Olga
O
Department of Physiology and Biophysics, Boston University School of Medicine, W329, 715 Albany Street, Boston MA 02118, USA. Gursky@bu.edu
D053302:Apolipoprotein C-I / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D053302:Apolipoprotein C-I; D010743:Phospholipids