Binding of alpha1-acid glycoprotein to membrane results in a unique structural change and ligand release.
Alpha(1)-acid glycoprotein (AGP) consists of 183 amino acid residues and 5 carbohydrate chains and binds to basic and neutral drugs as well as steroid hormones. We investigated the structural properties and ligand-binding capacity of AGP under mild acidic conditions and its interactions with liposomes prepared from neutral or anionic lipids and the neutral drug, progesterone. Interestingly, AGP had a unique structure at pH 4.5, at which the tertiary structure changed, whereas the secondary structure remained intact. Furthermore, the binding capacity of AGP for progesterone did not significantly change under these conditions. It was also observed that AGP was strongly bound to the anionic membrane at pH 4.5, forming an alpha-helix-rich structure from the original beta-sheet-rich structure, which significantly decreased the binding capacity of AGP for progesterone. The structural transitions as well as the membrane binding were suppressed by adding NaCl. These results indicate that AGP has a unique structure on the membrane surface under mild acidic conditions. The conformational change induces binding to the membrane aided by electrostatic interaction, and AGP subsequently takes on a predominantly alpha-helical conformation.
Graduate School of Pharmaceutical Science, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Koji
K
Nishi
Toru
T
Maruyama
H Brian
HB
Halsall
Tetsuro
T
Handa
Masaki
M
Otagiri
D000143:Acids / Q000737:chemistry; D001665:Binding Sites; D002462:Cell Membrane; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D009961:Orosomucoid / Q000737:chemistry* / Q000378:metabolism*; D011374:Progesterone / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012965:Sodium Chloride / Q000494:pharmacology; D055672:Static Electricity
D000143:Acids; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D009961:Orosomucoid; D012965:Sodium Chloride; D011374:Progesterone