Bakshi Kunal, Mercier Richard W, Pavlopoulos Spiro
Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, U-3092, Storrs, CT 06269, USA.
FEBS Lett. 2007 Oct 16;581(25):5009-16. doi: 10.1016/j.febslet.2007.09.030. Epub 2007 Sep 24.
Desensitization of the cannabinoid CB1 receptor is mediated by the interaction with arrestin. In this study, we report the structural changes of a synthetic diphosphorylated peptide corresponding to residues 419-439 of the CB1 C-terminus upon binding to arrestin-2. This segment is pivotal to the desensitization of CB1. Using high-resolution proton NMR, we observe two helical segments in the bound peptide that are separated by the presence a glycine residue. The binding we observe is with a diphoshorylated peptide, whereas a previous study reported binding of a highly phosphorylated rhodopsin fragment to visual arrestin. The arrestin bound conformations of the peptides are compared.
大麻素CB1受体的脱敏作用是由与抑制蛋白的相互作用介导的。在本研究中,我们报告了与CB1 C末端419 - 439位残基对应的合成双磷酸化肽在与抑制蛋白-2结合时的结构变化。该片段对CB1的脱敏作用至关重要。使用高分辨率质子核磁共振,我们在结合肽中观察到两个螺旋片段,它们被一个甘氨酸残基隔开。我们观察到的结合是与双磷酸化肽的结合,而先前的一项研究报道了高度磷酸化的视紫红质片段与视觉抑制蛋白的结合。对肽与抑制蛋白结合的构象进行了比较。