Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.
Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.
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DOI：
10.1016/j.chom.2012.06.005
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发表时间：
2012-08-16
影响因子：
30.3
通讯作者：
Rayner JC
中科院分区：
文献类型：
--
作者：
Jones ML;Collins MO;Goulding D;Choudhary JS;Rayner JC
恶性疟原虫在人红细胞中进行无性繁殖并经历严格调控的发育过程。参与调节该过程的一种机制是寄生虫蛋白的翻译后修饰（PTM）。棕榈酰化是一种半胱氨酸残基发生可逆脂质修饰的PTM，可以通过多种方式调节靶蛋白。使用互补的棕榈酰蛋白纯化方法和定量质谱，我们研究了蛋白质棕榈酰化无性阶段恶性疟原虫，并确定了400多个棕榈酰化的蛋白质，包括那些参与细胞粘附，耐药性，信号，发展和入侵。与棕榈酰化蛋白的流行一致，棕榈酰化对于恶性疟原虫无性发育是必需的，并且通过直接调节肌动蛋白-肌球蛋白侵袭马达的组分的稳定性来影响红细胞侵袭。此外，恶性疟原虫以不同的方式使用棕榈酰化，稳定地修饰一些蛋白质，同时动态地棕榈酰化其他蛋白质。因此，棕榈酰化在调节恶性疟原虫血液阶段发育中起核心作用。一种全球性的方法在恶性疟原虫中鉴定了>400种棕榈酰化蛋白质棕榈酰化蛋白质是入侵和其他毒力相关过程的核心棕榈酰化是完成恶性疟原虫无性生命周期所必需的
Asexual stage Plasmodium falciparum replicates and undergoes a tightly regulated developmental process in human erythrocytes. One mechanism involved in the regulation of this process is posttranslational modification (PTM) of parasite proteins. Palmitoylation is a PTM in which cysteine residues undergo a reversible lipid modification, which can regulate target proteins in diverse ways. Using complementary palmitoyl protein purification approaches and quantitative mass spectrometry, we examined protein palmitoylation in asexual-stage P. falciparum parasites and identified over 400 palmitoylated proteins, including those involved in cytoadherence, drug resistance, signaling, development, and invasion. Consistent with the prevalence of palmitoylated proteins, palmitoylation is essential for P. falciparum asexual development and influences erythrocyte invasion by directly regulating the stability of components of the actin-myosin invasion motor. Furthermore, P. falciparum uses palmitoylation in diverse ways, stably modifying some proteins while dynamically palmitoylating others. Palmitoylation therefore plays a central role in regulating P. falciparum blood stage development. ► A global approach identified >400 palmitoylated proteins in Plasmodium falciparum ► Palmitoyl proteins are central to invasion and other virulence-associated processes ► Palmitoylation is required for completion of the P. falciparum asexual life cycle ► P. falciparum uses palmitoylation dynamically for diverse regulatory purposes
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
15.3
作者：
Naik, RS;Branch, OH;Gowda, DC
通讯作者：
Gowda, DC
影响因子：
64.8
作者：
Lasonder, E;Ishihama, Y;Mann, M
通讯作者：
Mann, M
影响因子：
4.8
作者：
Baum, J;Richard, D;Cowman, AF
通讯作者：
Cowman, AF
影响因子：
1.5
作者：
Rees-Channer, Roxanne R.;Martin, Stephen R.;Holder, Anthony A.
通讯作者：
Holder, Anthony A.