刚地弓形虫中棕榈酰化蛋白的全局分析
Global Analysis of Palmitoylated Proteins in Toxoplasma gondii.
作者信息
Foe Ian T, Child Matthew A, Majmudar Jaimeen D, Krishnamurthy Shruthi, van der Linden Wouter A, Ward Gary E, Martin Brent R, Bogyo Matthew
机构信息
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Cell Host Microbe. 2015 Oct 14;18(4):501-11. doi: 10.1016/j.chom.2015.09.006.
Post-translational modifications (PTMs) such as palmitoylation are critical for the lytic cycle of the protozoan parasite Toxoplasma gondii. While palmitoylation is involved in invasion, motility, and cell morphology, the proteins that utilize this PTM remain largely unknown. Using a chemical proteomic approach, we report a comprehensive analysis of palmitoylated proteins in T. gondii, identifying a total of 282 proteins, including cytosolic, membrane-associated, and transmembrane proteins. From this large set of palmitoylated targets, we validate palmitoylation of proteins involved in motility (myosin light chain 1, myosin A), cell morphology (PhIL1), and host cell invasion (apical membrane antigen 1, AMA1). Further studies reveal that blocking AMA1 palmitoylation enhances the release of AMA1 and other invasion-related proteins from apical secretory organelles, suggesting a previously unrecognized role for AMA1. These findings suggest that palmitoylation is ubiquitous throughout the T. gondii proteome and reveal insights into the biology of this important human pathogen.
翻译后修饰（PTMs），如棕榈酰化，对于原生动物寄生虫刚地弓形虫的裂解周期至关重要。虽然棕榈酰化参与侵袭、运动和细胞形态，但利用这种翻译后修饰的蛋白质在很大程度上仍不清楚。我们采用化学蛋白质组学方法，对刚地弓形虫中的棕榈酰化蛋白质进行了全面分析，共鉴定出282种蛋白质，包括胞质、膜相关和跨膜蛋白。从这一大组棕榈酰化靶点中，我们验证了参与运动（肌球蛋白轻链1、肌球蛋白A）、细胞形态（PhIL1）和宿主细胞侵袭（顶膜抗原1、AMA1）的蛋白质的棕榈酰化。进一步研究表明，阻断AMA1的棕榈酰化可增强AMA1和其他侵袭相关蛋白从顶端分泌细胞器的释放，这表明AMA1具有以前未被认识到的作用。这些发现表明棕榈酰化在刚地弓形虫蛋白质组中普遍存在，并揭示了对这种重要人类病原体生物学特性的见解。
Zotero 插件