How integration of positive and negative regulatory signals by a STAND signaling protein depends on ATP hydrolysis.
The role of nucleotide hydrolysis in signaling by signal transduction ATPases with numerous domains (STAND) is poorly understood. Here we use MalT, the transcription activator of the Escherichia coli maltose regulon, as a model system to address this question. We have constructed the MalT-D129A variant that binds ATP but does not hydrolyze it and have characterized it in vivo and in vitro. ATP hydrolysis is not essential for transcription activation but is crucial in controlling MalT activity. MalT cycles between an ADP-bound, resting form that is the target of negative effectors and an ATP-bound, active form, which oligomerizes. Conversion to the active form involves nucleotide exchange and depends on maltotriose binding, whereas resetting to the inactive state relies on ATP hydrolysis, which ensues MalT multimerization. Such a controlled binary switch most likely applies to the other STAND NTPases, including Apaf-1 and the human innate immunity proteins NOD2, and CIAS1.
Marquenet
Emélie
E
Unité de Génétique Moléculaire, CNRS URA 2172, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Richet
Evelyne
E
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D006868:Hydrolysis; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018085:Regulon; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014312:Trisaccharides / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C489398:MalK protein, E coli; C058976:MalT protein, E coli; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014312:Trisaccharides; C079405:MalY protein, E coli; D000244:Adenosine Diphosphate; C008317:maltotriose; D000255:Adenosine Triphosphate; D003542:Cystathionine gamma-Lyase