Andrés Anna, Garriga Pere, Manyosa Joan
Unitat de Biofísica, Departament de Bioquímica i de Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain.
Biochem Biophys Res Commun. 2003 Mar 28;303(1):294-301. doi: 10.1016/s0006-291x(03)00328-0.
Point mutations found in rhodopsin associated with the retinal degenerative disease retinitis pigmentosa have been expressed in mammalian COS-1 cells, purified, and characterised. The mutations characterised-most of them for the first time-have been Met44Thr, Gly114Asp, Arg135Leu, Val137Met, and Pro171Leu in the transmembrane domain; Leu328Pro and Ala346Pro in the C-terminal tail of the cytoplasmic domain; and Gly106Trp in the intradiscal domain. Several of these mutations cause misfolding which results in impaired 11-cis-retinal binding. Two of them, Met44Thr and Val137Met, show spectral and structural features similar to those of wild type rhodopsin (Type I mutants) but significantly increased transducin initial activation rates. We propose that, in the case of these mutants, abnormal functioning resulting in faster activation kinetics could also play a role in retinitis pigmentosa by altering the stoichiometric balance of the different proteins involved in the phototransduction biochemical reactions.
在与视网膜退行性疾病色素性视网膜炎相关的视紫红质中发现的点突变已在哺乳动物COS-1细胞中表达、纯化并进行了表征。已表征的突变——其中大多数是首次表征——包括跨膜结构域中的Met44Thr、Gly114Asp、Arg135Leu、Val137Met和Pro171Leu；细胞质结构域C末端尾巴中的Leu328Pro和Ala346Pro；以及盘内结构域中的Gly106Trp。这些突变中有几个会导致错误折叠，从而导致11-顺式视黄醛结合受损。其中两个，Met44Thr和Val137Met，显示出与野生型视紫红质相似的光谱和结构特征（I型突变体），但转导素的初始激活率显著增加。我们提出，对于这些突变体，导致更快激活动力学的异常功能也可能通过改变光转导生化反应中涉及的不同蛋白质的化学计量平衡而在色素性视网膜炎中起作用。
