Mackenzie S M, Brooker M R, Gill T R, Cox G B, Howells A J, Ewart G D
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, The Australian National University, P.O. Box 4, Canberra City 0200, Australia.
Biochim Biophys Acta. 1999 Jul 15;1419(2):173-85. doi: 10.1016/s0005-2736(99)00064-4.
The white, brown and scarlet genes of Drosophila melanogaster encode proteins which transport guanine or tryptophan (precursors of the red and brown eye colour pigments) and belong to the ABC transporter superfamily. Current models envisage that the white and brown gene products interact to form a guanine specific transporter, while white and scarlet gene products interact to form a tryptophan transporter. In this study, we report the nucleotide sequence of the coding regions of five white alleles isolated from flies with partially pigmented eyes. In all cases, single amino acid changes were identified, highlighting residues with roles in structure and/or function of the transporters. Mutations in w(cf) (G589E) and w(sat) (F590G) occur at the extracellular end of predicted transmembrane helix 5 and correlate with a major decrease in red pigments in the eyes, while brown pigments are near wild-type levels. Therefore, those residues have a more significant role in the guanine transporter than the tryptophan transporter. Mutations identified in w(crr) (H298N) and w(101) (G243S) affect amino acids which are highly conserved among the ABC transporter superfamily within the nucleotide binding domain. Both cause substantial and similar decreases of red and brown pigments indicating that both tryptophan and guanine transport are impaired. The mutation identified in w(Et87) alters an amino acid within an intracellular loop between transmembrane helices 2 and 3 of the predicted structure. Red and brown pigments are reduced to very low levels by this mutation indicating this loop region is important for the function of both guanine and tryptophan transporters.
果蝇的白色、棕色和猩红色基因编码的蛋白质负责转运鸟嘌呤或色氨酸（红色和棕色眼色素的前体），属于ABC转运蛋白超家族。目前的模型认为，白色和棕色基因产物相互作用形成一种鸟嘌呤特异性转运蛋白，而白色和猩红色基因产物相互作用形成一种色氨酸转运蛋白。在本研究中，我们报告了从部分色素沉着眼睛的果蝇中分离出的五个白色等位基因编码区的核苷酸序列。在所有情况下，都鉴定出了单个氨基酸变化，突出了在转运蛋白结构和/或功能中起作用的残基。w(cf)（G589E）和w(sat)（F590G）中的突变发生在预测的跨膜螺旋5的细胞外末端，与眼睛中红色素的大幅减少相关，而棕色色素接近野生型水平。因此，这些残基在鸟嘌呤转运蛋白中比在色氨酸转运蛋白中发挥更重要的作用。在w(crr)（H298N）和w(101)（G243S）中鉴定出的突变影响了核苷酸结合域内ABC转运蛋白超家族中高度保守的氨基酸。两者都导致红色和棕色色素大幅且相似地减少，表明色氨酸和鸟嘌呤的转运都受到损害。在w(Et87)中鉴定出的突变改变了预测结构中跨膜螺旋2和3之间细胞内环内的一个氨基酸。这种突变使红色和棕色色素减少到非常低的水平，表明该环区域对鸟嘌呤和色氨酸转运蛋白的功能都很重要。
