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西方施万酵母的SCR1基因编码一种高度疏水的多肽,该多肽赋予核糖体对放线菌酮的抗性。

The SCR1 gene from Schwanniomyces occidentalis encodes a highly hydrophobic polypeptide, which confers ribosomal resistance to cycloheximide.

作者信息

Hoenicka Janet, Fernández Lobato María, Marín Dolores, Jiménez Antonio

机构信息

Centro de Biología Molecular, Universidad Autónoma de Madrid, Canto Blanco, 28049 Madrid, Spain.

出版信息

Yeast. 2002 Jun 30;19(9):735-43. doi: 10.1002/yea.871.

Abstract

In Saccharomyces cerevisiae, the SCR1 gene from Schwanniomyces occidentalis is known to induce ribosomal resistance to cycloheximide (cyh). A 2.8 kb DNA fragment encoding this gene was sequenced. Its EMBL Accession No. is AJ419770. It disclosed a putative tRNA(Asn) (GUU) sequence located downstream of an open reading frame (ORF) of 1641 nucleotides. This ORF was shown to correspond to SCR1. It would encode a highly hydrophobic polypeptide (SCR1) with 12 transmembrane domains. SCR1 is highly similar to a variety of yeast proteins of the multidrug-resistance (MDR) family. However, SCR1 only conferred resistance to cyh but not to benomyl or methotrexate. The cyh-resistance phenotype induced by SCR1 was confirmed in several S. cerevisiae strains that expressed this gene to reside at the ribosomal level. In contrast, a beta-galacosidase-tagged SCR1 was found to be integrated in the endoplasmic reticulum (ER). It is proposed that the ribosomes of yeast cells expressing SCR1 undergo a conformational change during their interaction with the ER, which lowers their affinity for cyh-binding. If so, these findings would disclose a novel ribosomal resistance mechanism.

摘要

在酿酒酵母中,已知西方施万酵母的SCR1基因可诱导核糖体对环己酰亚胺(cyh)产生抗性。对编码该基因的一个2.8 kb DNA片段进行了测序。其EMBL登录号为AJ419770。该片段揭示了一个推定的tRNA(Asn)(GUU)序列,位于一个1641个核苷酸的开放阅读框(ORF)下游。该ORF被证明对应于SCR1。它将编码一个具有12个跨膜结构域的高度疏水多肽(SCR1)。SCR1与多种多药耐药(MDR)家族的酵母蛋白高度相似。然而,SCR1仅赋予对cyh的抗性,而不赋予对苯菌灵或甲氨蝶呤的抗性。在几个表达该基因的酿酒酵母菌株中,证实了SCR1诱导的cyh抗性表型存在于核糖体水平。相反,发现一个β-半乳糖苷酶标记的SCR1整合在内质网(ER)中。有人提出,表达SCR1的酵母细胞核糖体在与ER相互作用期间会发生构象变化,这降低了它们对cyh结合的亲和力。如果是这样,这些发现将揭示一种新的核糖体抗性机制。

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