视紫红质的结构与功能：对视盘内半胱氨酸（Cys-110、-185和-187）在视紫红质折叠和功能中作用的进一步阐释。
Structure and function in rhodopsin: further elucidation of the role of the intradiscal cysteines, Cys-110, -185, and -187, in rhodopsin folding and function.
作者信息
Hwa J, Reeves P J, Klein-Seetharaman J, Davidson F, Khorana H G
机构信息
Departments of Biology and Chemistry, Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1932-5. doi: 10.1073/pnas.96.5.1932.
Abstract
The disulfide bond between Cys-110 and Cys-187 in the intradiscal domain is required for correct folding in vivo and function of mammalian rhodopsin. Misfolding in rhodopsin, characterized by the loss of ability to bind 11-cis-retinal, has been shown to be caused by an intradiscal disulfide bond different from the above native disulfide bond. Further, naturally occurring single mutations of the intradiscal cysteines (C110F, C110Y, and C187Y) are associated with retinitis pigmentosa (RP). To elucidate further the role of every one of the three intradiscal cysteines, mutants containing single-cysteine replacements by alanine residues and the above three RP mutants have been studied. We find that C110A, C110F, and C110Y all form a disulfide bond between C185 and C187 and cause loss of retinal binding. C185A allows the formation of a C110-C187 disulfide bond, with wild-type-like rhodopsin phenotype. C187A forms a disulfide bond between C110 and C185 and binds retinal, and the pigment formed has markedly altered bleaching behavior. However, the opsin from the RP mutant C187Y forms no rhodopsin chromophore.
摘要
椎间盘内区域中半胱氨酸-110（Cys-110）和半胱氨酸-187（Cys-187）之间的二硫键是哺乳动物视紫红质在体内正确折叠和发挥功能所必需的。视紫红质的错误折叠表现为失去结合11-顺式视黄醛的能力，已证明这是由一种不同于上述天然二硫键的椎间盘内二硫键引起的。此外，椎间盘内半胱氨酸的自然发生的单突变（C110F、C110Y和C187Y）与色素性视网膜炎（RP）相关。为了进一步阐明三个椎间盘内半胱氨酸各自的作用，研究了用丙氨酸残基替换单个半胱氨酸的突变体以及上述三个RP突变体。我们发现，C110A、C110F和C110Y均在C185和C187之间形成二硫键，并导致视黄醛结合丧失。C185A允许形成C110-C187二硫键，具有野生型样视紫红质表型。C187A在C110和C185之间形成二硫键并结合视黄醛，形成的色素具有明显改变的漂白行为。然而，RP突变体C187Y的视蛋白不形成视紫红质发色团。
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