TY - JOUR
T1 - De-AMPylation unmasked
T2 - Modulation of host membrane trafficking
AU - Ham, Hyeilin
AU - Orth, Kim
PY - 2011/10/11
Y1 - 2011/10/11
N2 - 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.
AB - 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.
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U2 - 10.1126/scisignal.2002458
DO - 10.1126/scisignal.2002458
M3 - Review article
C2 - 21990428
AN - SCOPUS:80054050157
SN - 1945-0877
VL - 4
JO - Science signaling
JF - Science signaling
IS - 194
M1 - pe42
ER -