Rao V R, Oprian D D
Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254, USA.
Annu Rev Biophys Biomol Struct. 1996;25:287-314. doi: 10.1146/annurev.bb.25.060196.001443.
Rhodopsin, the visual pigment of rod photoreceptors cells, is a member of the large family of G protein-coupled receptors. Rhodopsin is composed of two parts: a polypeptide chain called opsin and an 11-cis-retinal chromophore covalently bound to the protein by means of a protonated Schiff base linkage to Lys296 located in the seventh transmembrane segment of the protein. Several mutations have been described that constitutively activate the apoprotein opsin. These mutations appear to activate the protein by a common mechanism of action. They disrupt a salt-bridge between Lys296 and the couterion Glu113 that helps constrain the protein to an inactive conformation. Four of the mutations have been shown to cause two different diseases of the retina, retinitis pigmentosa and congenital night blindness. Recently, several other human diseases have been shown to be caused by constitutively activating mutations of G protein-coupled receptors.
视紫红质是视杆光感受器细胞的视觉色素，是G蛋白偶联受体大家族的一员。视紫红质由两部分组成：一条称为视蛋白的多肽链和一个11-顺式视黄醛发色团，该发色团通过质子化席夫碱连接与位于蛋白质第七跨膜段的赖氨酸296共价结合。已经描述了几种组成性激活脱辅基蛋白视蛋白的突变。这些突变似乎通过一种共同的作用机制激活蛋白质。它们破坏了赖氨酸296和反离子谷氨酸113之间的盐桥，该盐桥有助于将蛋白质限制在无活性构象。其中四种突变已被证明会导致两种不同的视网膜疾病，色素性视网膜炎和先天性夜盲症。最近，其他几种人类疾病已被证明是由G蛋白偶联受体的组成性激活突变引起的。
