Kuchler K, Sterne R E, Thorner J
Department of Biochemistry, University of California, Berkeley 94720.
EMBO J. 1989 Dec 20;8(13):3973-84. doi: 10.1002/j.1460-2075.1989.tb08580.x.
Saccharomyces cerevisiae MATa cells release a lipopeptide mating pheromone, a-factor. Radiolabeling and immunoprecipitation show that MATa ste6 mutants produce pro-a-factor and mature a-factor intracellularly, but little or no extracellular pheromone. Normal MATa cells carrying a multicopy plasmid containing both MFa1 (pro-a-factor structural gene) and the STE6 gene secrete a-factor at least five times faster than the same cells carrying only MFa1 in the same vector. The nucleotide sequence of the STE6 gene predicts a 1290 residue polypeptide with multiple membrane spanning segments and two hydrophilic domains, each strikingly homologous to a set of well-characterized prokaryotic permeases (including hlyB, oppD, hisP, malK and pstB) and sharing even greater identity with mammalian mdr (multiple drug resistance) transporters. These results suggest that the STE6 protein in yeast, and possibly mdr in animals, is a transmembrane translocator that exports polypeptides by a route independent of the classical secretory pathway.
酿酒酵母MATa细胞释放一种脂肽交配信息素，即a因子。放射性标记和免疫沉淀表明，MATa ste6突变体在细胞内产生前体a因子和成熟a因子，但细胞外信息素很少或没有。携带含有MFa1（前体a因子结构基因）和STE6基因的多拷贝质粒的正常MATa细胞分泌a因子的速度至少比在同一载体中仅携带MFa1的相同细胞快五倍。STE6基因的核苷酸序列预测有一个1290个残基的多肽，具有多个跨膜区段和两个亲水区段，每个区段都与一组特征明确的原核通透酶（包括hlyB、oppD、hisP、malK和pstB）显著同源，并且与哺乳动物的多药耐药（mdr）转运蛋白有更高的同源性。这些结果表明，酵母中的STE6蛋白，可能还有动物中的mdr，是一种跨膜转运体，通过一条独立于经典分泌途径的途径输出多肽。
