Smyth K A, Belote J M
Department of Biology, Syracuse University, Syracuse, New York 13244, USA.
Genetics. 1999 Jan;151(1):211-20. doi: 10.1093/genetics/151.1.211.
Proteasomes are multicatalytic complexes that function as the major proteolytic machinery in regulated protein degradation. The eukaryotic 20S proteasome proteolytic core structure comprises 14 different subunits: 7 alpha-type and 7 beta-type. DTS7 is a dominant temperature-sensitive (DTS) lethal mutation at 29 degrees that also acts as a recessive lethal at ambient temperatures. DTS7 maps to cytological position 71AB. Molecular characterization of DTS7 reveals that this is caused by a missense mutation in a beta-type subunit gene, beta2. A previously characterized DTS mutant, l(3)73Ai1, results from a missense mutation in another beta-type subunit gene, beta6. These two mutants share a very similar phenotype, show a strong allele-specific genetic interaction, and are rescued by the same extragenic suppressor, Su(DTS)-1. We propose that these mutants might act as "poison subunits," disrupting proteasome function in a dosage-dependent manner, and suggest how they may interact on the basis of the structure of the yeast 20S proteasome.
蛋白酶体是多催化复合物，在调节蛋白质降解中作为主要的蛋白水解机制发挥作用。真核生物的20S蛋白酶体蛋白水解核心结构由14个不同的亚基组成：7个α型亚基和7个β型亚基。DTS7是一个在29摄氏度时具有显性温度敏感性（DTS）致死突变，在环境温度下也表现为隐性致死。DTS7定位于细胞学位置71AB。DTS7的分子特征表明，这是由β型亚基基因beta2中的一个错义突变引起的。一个先前已鉴定的DTS突变体l(3)73Ai1是由另一个β型亚基基因beta6中的错义突变导致的。这两个突变体具有非常相似的表型，表现出强烈的等位基因特异性遗传相互作用，并被同一个基因外抑制子Su(DTS)-1拯救。我们提出，这些突变体可能作为“毒性亚基”，以剂量依赖的方式破坏蛋白酶体功能，并根据酵母20S蛋白酶体的结构提出它们可能的相互作用方式。
