Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sci Signal. 2011 Oct 11;4(194):pe42. doi: 10.1126/scisignal.2002458.
AMPylation, a posttranslational modification in which adenosine monophosphate (AMP) is added to hydroxyl side chains of protein substrates, is employed by many bacterial pathogens to subvert host signaling pathways during infection. The Legionella pneumophila effector protein SidM is a multifunctional enzyme that targets the guanosine triphosphatase (GTPase) Rab1 to manipulate intracellular vesicular trafficking in the host cell. SidM recruits Rab1 to the membranes of Legionella-containing vacuoles and activates Rab1 through its guanine nucleotide exchange factor activity. SidM then AMPylates Rab1, converting it into a constitutively active form that cannot be accessed by LepB, a GTPase-activating protein that is secreted by L. pneumophila. However, the molecular event that eventually leads to Rab1 inactivation and subsequent removal from Legionella-containing vacuoles has remained unknown. New evidence has identified SidD as a de-AMPylase that removes AMP from Rab1, which enables its inactivation by LepB later during the infection process. This finding demonstrates a complete pathway of reversible modifications regulated by specific bacterial enzymes to modulate host membrane trafficking.
AMP 酰化是一种将单磷酸腺苷（AMP）添加到蛋白质底物的羟基侧链上的翻译后修饰，许多细菌病原体在感染过程中利用这种修饰来颠覆宿主信号通路。嗜肺军团菌效应蛋白 SidM 是一种多功能酶，它靶向鸟苷三磷酸酶（GTPase）Rab1，以操纵宿主细胞内的囊泡运输。SidM 将 Rab1 招募到含有军团菌的空泡的膜上，并通过其鸟嘌呤核苷酸交换因子活性激活 Rab1。然后，SidM 对 Rab1 进行 AMP 酰化，将其转化为不可被 LepB （一种由嗜肺军团菌分泌的 GTPase 激活蛋白）访问的组成型激活形式。然而，最终导致 Rab1 失活并随后从含有军团菌的空泡中去除的分子事件仍然未知。新的证据表明，SidD 是一种去 AMP 酶，它从 Rab1 上去除 AMP，这使得 LepB 能够在感染过程中的后期使其失活。这一发现展示了一条受特定细菌酶调控的可逆修饰的完整途径，用于调节宿主膜运输。
