Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
Int J Mol Sci. 2020 Jul 3;21(13):4742. doi: 10.3390/ijms21134742.
Infectious proteins (prions) include an array of human (mammalian) and yeast amyloid diseases in which a protein or peptide forms a linear β-sheet-rich filament, at least one functional amyloid prion, and two functional infectious proteins unrelated to amyloid. In at least eight anti-prion systems deal with pathogenic amyloid yeast prions by (1) blocking their generation (Ssb1,2, Ssz1, Zuo1), (2) curing most variants as they arise (Btn2, Cur1, Hsp104, Upf1,2,3, Siw14), and (3) limiting the pathogenicity of variants that do arise and propagate (Sis1, Lug1). Known mechanisms include facilitating proper folding of the prion protein (Ssb1,2, Ssz1, Zuo1), producing highly asymmetric segregation of prion filaments in mitosis (Btn2, Hsp104), competing with the amyloid filaments for prion protein monomers (Upf1,2,3), and regulation of levels of inositol polyphosphates (Siw14). It is hoped that the discovery of yeast anti-prion systems and elucidation of their mechanisms will facilitate finding analogous or homologous systems in humans, whose manipulation may be useful in treatment.
传染性蛋白质（朊病毒）包括一系列人类（哺乳动物）和酵母淀粉样蛋白疾病，其中蛋白质或肽形成线性β-片层丰富的纤维，至少有一种功能性淀粉样蛋白朊病毒，以及两种与淀粉样蛋白无关的功能性传染性蛋白质。在至少 8 个抗朊病毒系统中，通过以下方式来处理致病性的酵母淀粉样蛋白朊病毒：（1）阻止它们的产生（Ssb1、2、Ssz1、Zuo1）；（2）在它们出现时消除大多数变体（Btn2、Cur1、Hsp104、Upf1、2、3、Siw14）；（3）限制出现和传播的变体的致病性（Sis1、Lug1）。已知的机制包括促进朊病毒蛋白的正确折叠（Ssb1、2、Ssz1、Zuo1），产生有丝分裂中朊病毒纤维的高度不对称分离（Btn2、Hsp104），与淀粉样蛋白纤维竞争朊病毒蛋白单体（Upf1、2、3），以及调节肌醇多磷酸的水平（Siw14）。希望发现酵母抗朊病毒系统及其阐明其机制将有助于在人类中发现类似或同源的系统，其操纵可能对治疗有用。
