Cooperative effect of hydrophobic and electrostatic forces on alcohol‐induced α‐helix formation of α₁‐acid glycoprotein

Abstract

a 1 -Acid glycoprotein (AGP) is a serum glycoprotein that mainly binds basic drugs. Previous reports have shown that AGP converts from a b-sheet to an a-helix upon interaction with biomembranes. In the current studies, we found that alkanols, diols, and halogenols all induce this conformational change. Increased length and bulkiness of the hydrocarbon group and the presence of a halogen atom promoted this conversion, whereas the presence of a hydroxyl group inhibited it. Moreover, the effect was dependent on the hydrophobic and electrostatic properties of the alcohols. These results indicate that, in a membrane environment, hydrophobic and electrostatic factors cooperatively induce the transition of AGP from a b-sheet to an a-helix.

Involvement of disulfide bonds and histidine 172 in a unique β‐sheet to α‐helix transition of α1‐acid glycoprotein at the biomembrane interface

“…However, RA‐AGP showed a far CD spectrum similar to that observed in the interactions with various biomembrane models 18–20. Table II shows the α‐helix contents of RA‐AGP and AGP interacted with biomembrane models reported previously (native state, 40% methanol at pH 4.0, and the anionic liposomes at pH 4.5),18–20 and predicted from the amino acid sequence using several programs 56–62. RA‐AGP showed the α‐helix content similar to that of AGP interacted with a biomembrane model and that predicted from the amino acid sequence (Table II).…”

“…Why does AGP appear to function intracellularly, despite the fact that it is most commonly found in the blood? In addition to our previous report on the interaction of AGP with biomembrane models,18–20 Andersen detected AGP on the surface of normal human lymphocytes, granulocytes, and monocytes, using fluorescent electron microscopy 14, 15. Indeed, there are reports that AGP interacts with leukocytes and then exhibit various pharmacological actions 11.…”

“…Interestingly, RA‐AGP showed a far CD spectrum similar to that of AGP interacted with membrane models 18–20. The near UV CD spectral results indicate that the tertiary structure of RA‐AGP is significantly different from that of AGP.…”

“…We previously reported that AGP interacts with reverse micelles, liposomes, and alcohols used as models of biomembranes, followed by the conformational transition of AGP from the β‐sheet form to the α‐helix form18–20 We also found that hydrophobic and electrostatic interactions with the biomembrane were cooperatively involved in α‐helix formation of AGP. However, intramolecular factors concerned in the transition to such α‐helix structure have not been clarified at all.…”

“…We previously reported that the interaction between AGP and biomembrane models (reverse micelles, liposomes, and alcohols) resulted in a structural change and a decrease in ligand‐binding capacity 18–20. Moreover, this interaction resulted in a unique conformational transition from a β‐sheet structure to an α‐helix structure.…”