title: Energetics of lipid binding in a hydrophobic protein cavity.
abstract: Hydrophobic bonding is central to many biochemical processes, such as protein folding and association. However, a complete description of the forces underlying hydrophobic interactions is lacking. The goal of this study was to evaluate the intrinsic energetic contributions of -CH(3), >CH(2), and -HC═CH- groups to protein-lipid binding. To this end, Arrhenius parameters were measured for dissociation of gaseous deprotonated ions (at the -7 charge state) of complexes of bovine β-lactoglobulin (Lg), a model lipid-binding protein, and a series of saturated, unsaturated, and branched fatty acids (FA). In the gas phase, the (Lg + FA)(7-) ions adopt one of two noninterconverting structures, which we refer to as the fast and slow dissociating components. The dissociation activation energies measured for the fast components of the (Lg + FA)(7-) ions were found to correlate linearly with the association free energies measured in aqueous solution, suggesting that the specific protein-lipid interactions are preserved in the gas phase. The average contributions that the -CH(3), >CH(2), and -HC═CH- groups make to the dissociation activation energies measured for the fast components of the (Lg + FA)(7-) ions were compared with enthalpies for the transfer of hydrocarbons from the gas phase to organic solvents. For >CH(2) groups, the interior of the cavity was found to most closely resemble the relatively polar solvents acetone and N,N-dimethylformamide, which have dielectric constants (ε) of 21 and 39, respectively. For -CH(3) groups, the solvent environment most closely resembles 1-butanol (ε = 17), although the energetic contribution is dependent on the location of the methyl group in the FA. In contrast, the solvation of -HC═CH- groups is similar to that afforded by the nonpolar solvent cyclohexane (ε = 2).
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.forename: Klaus
authors.initials: K
authors.lastname: Michelsen
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kitova
authors.forename: Paul D
authors.initials: PD
authors.lastname: Schnier
authors.forename: John S
authors.initials: JS
authors.lastname: Klassen
mesh_terms: D000096:Acetone / Q000737:chemistry; D000818:Animals; D002244:Carbon / Q000737:chemistry; D002417:Cattle; D005227:Fatty Acids / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions; D007782:Lactoglobulins / Q000737:chemistry; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D011485:Protein Binding; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D020349:Surface Plasmon Resonance; D014867:Water / Q000737:chemistry
chemical_list: D005227:Fatty Acids; D007477:Ions; D007782:Lactoglobulins; D008024:Ligands; D008055:Lipids; D011506:Proteins; D012997:Solvents; D014867:Water; D000096:Acetone; D002244:Carbon