Tayeb-Fligelman Einav, Tabachnikov Orly, Moshe Asher, Goldshmidt-Tran Orit, Sawaya Michael R, Coquelle Nicolas, Colletier Jacques-Philippe, Landau Meytal
Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Department of Biological Chemistry, Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Science. 2017 Feb 24;355(6327):831-833. doi: 10.1126/science.aaf4901.
Amyloids are ordered protein aggregates, found in all kingdoms of life, and are involved in aggregation diseases as well as in physiological activities. In microbes, functional amyloids are often key virulence determinants, yet the structural basis for their activity remains elusive. We determined the fibril structure and function of the highly toxic, 22-residue phenol-soluble modulin α3 (PSMα3) peptide secreted by PSMα3 formed elongated fibrils that shared the morphological and tinctorial characteristics of canonical cross-β eukaryotic amyloids. However, the crystal structure of full-length PSMα3, solved de novo at 1.45 angstrom resolution, revealed a distinctive "cross-α" amyloid-like architecture, in which amphipathic α helices stacked perpendicular to the fibril axis into tight self-associating sheets. The cross-α fibrillation of PSMα3 facilitated cytotoxicity, suggesting that this assembly mode underlies function in .
淀粉样蛋白是有序的蛋白质聚集体，存在于所有生物界，与聚集性疾病以及生理活动都有关联。在微生物中，功能性淀粉样蛋白通常是关键的毒力决定因素，但其活性的结构基础仍然难以捉摸。我们确定了由[具体微生物名称]分泌的剧毒22个残基的酚溶性调节素α3（PSMα3）肽的原纤维结构和功能，PSMα3形成了细长的原纤维，其具有典型的交叉β真核淀粉样蛋白的形态和染色特征。然而，全长PSMα3的晶体结构在1.45埃分辨率下从头解析，揭示了一种独特的“交叉α”淀粉样蛋白样结构，其中两亲性α螺旋垂直于原纤维轴堆叠成紧密的自缔合片层。PSMα3 的交叉α纤维化促进了细胞毒性，表明这种组装模式是其在[具体生理活动或疾病过程]中功能的基础。
