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首页> 外文期刊>Biochemistry >Phospholipid Bicelles Improve the Conformational Stability of Rhodopsin Mutants Associated with Retinitis Pigmentosa
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Phospholipid Bicelles Improve the Conformational Stability of Rhodopsin Mutants Associated with Retinitis Pigmentosa

机译：磷脂Bicelles提高视色素突变体与视网膜色素变性相关的构象稳定性。

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摘要

Mutations in the visual photoreceptor rhodopsin are the cause of the retinal degenerative disease retinitis pigmentosa. Some naturally occurring mutations can lead to protein conformational instability. Two such mutations, NSSK and G90V, in the first and second transmembrane helices of the receptor, have been associated with sector and classical retinitis pigmentosa, respectively, and showed enhanced thermal sensitivity. We have carefully analyzed the effect of phospholipid bicelles on the stability and ligand binding properties of these two mutants and compared it with those of the detergent-solubilized samples. We have used a phospholipid bilayer consisting of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). We find that DMPC/DHPC 0 50 100 bicelles dramatically increase the thermal stability of the rhodopsin mutants G90V and N55K. The chromophore stability and regeneration of the mutants were also increased in bicelles when compared to their behavior in a dodecyl maltoside detergent solution. The retinal release process was slowed in bicelles, and chromophore entry, after illumination, was improved for the G90V mutant but not for N55K. Furthermore, fluorescence spectroscopy measurements showed that bicelles allowed more exogenous retinal binding to the photoactivated G90V mutant than in a detergent solution. In contrast, N55K could not reposition any chromophore either in the detergent or in bicelles. The results demonstrate that DMPC/DHPC bicelles can counteract the destabilizing effect of the disease-causing mutations and can modulate the structural changes in the ensuing receptor photoactivation in a distinct specific manner for different retinitis pigmentosa mutant phenotypes.
机译：视觉光感受器视紫红质的突变是视网膜变性疾病色素性视网膜炎的原因。一些自然发生的突变会导致蛋白质构象不稳定。受体的第一个和第二个跨膜螺旋中的两个这样的突变，NSSK和G90V，分别与扇形和经典性视网膜色素变性有关，并显示出增强的热敏感性。我们已经仔细分析了磷脂双细胞对这两个突变体的稳定性和配体结合特性的影响，并将其与去污剂溶解的样品进行了比较。我们已经使用了由1,2-二肉豆蔻酰基-sn-甘油-3-磷脂酰胆碱（DMPC）和1,2-二己酰基-sn-甘油-3-磷酸胆碱（DHPC）组成的磷脂双层。我们发现DMPC / DHPC 0 50 100 bicelles大大增加了视紫红质突变体G90V和N55K的热稳定性。与它们在十二烷基麦芽糖苷去污剂溶液中的行为相比，在双细胞中，发色团的发色团稳定性和再生也增加了。视网膜释放过程在双细胞中减慢了，光照后，G90V突变体的发色团进入得到了改善，但N55K却没有。此外，荧光光谱测量表明，与去污剂溶液相比，双细胞允许更多的外源性视网膜结合光活化的G90V突变体。相反，N55K不能在去污剂或双池中重新定位任何生色团。结果表明，DMPC / DHPC双细胞可以抵消致病突变的不稳定作用，并可以针对不同的视网膜色素变性突变体表型以独特的特异性方式调节随后的受体光活化的结构变化。

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