Zhorov B S, Ananthanarayanan V S
Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
J Biomol Struct Dyn. 1998 Feb;15(4):631-7. doi: 10.1080/07391102.1998.10508980.
Based on molecular modeling of the complexes between the mu-opioid receptor and its ligands, we present a hypothesis that accounts for several of the experimental data including the importance of conserved polar residues in rhodopsin-like G-protein-coupled receptors and the effect of Na+ on the binding of ligands to these receptors. We propose that agonists, but not antagonists, would displace Na+ from its initial binding site at the conserved D2.50 residue in the second transmembrane alpha-helical segment, H2. The displaced Na+ would pass through a "gate" of conserved hydrophobic residues and move along a tunnel-like interface (formed of H2, H3 and H7) enriched with several conserved hydrophilic residues including D3.49. Interaction of Na+ with D3.49 would result in the breaking of a salt-bridge between D3.49 and the conserved R3.50 residue thus exposing the latter for interaction with the G-protein.
基于μ-阿片受体与其配体之间复合物的分子模型，我们提出了一个假说，该假说解释了若干实验数据，包括视紫红质样G蛋白偶联受体中保守极性残基的重要性以及Na⁺对配体与这些受体结合的影响。我们提出，激动剂而非拮抗剂会将Na⁺从其在第二个跨膜α-螺旋段H2中保守的D2.50残基处的初始结合位点置换出来。被置换的Na⁺会穿过由保守疏水残基构成的“门”，并沿着富含包括D3.49在内的若干保守亲水残基的隧道状界面（由H2、H3和H7形成）移动。Na⁺与D3.49的相互作用会导致D3.49与保守的R3.50残基之间的盐桥断裂，从而使后者暴露出来与G蛋白相互作用。
