%0 Journal Article %T How 'arm-twisting' by the inducer triggers activation of the MalT transcription factor, a typical signal transduction ATPase with numerous domains (STAND) %+ Génétique Moléculaire %A Danot, Olivier %Z Agence Nationale de la Recherche (Grant number: ANR-08-BLAN-0204-01). Funding for open access charge: Institut Pasteur. %< avec comité de lecture %@ 0305-1048 %J Nucleic Acids Research %I Oxford University Press %V 43 %N 6 %P 3089-3099 %8 2015-03-31 %D 2015 %R 10.1093/nar/gkv158 %M 25740650 %K ATPase %K STAND %K signal transduction %K ligand binding %K chemical cross-linking %K disulfide bond %K maltotriose %K transcription activation %Z Life Sciences [q-bio] %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]Journal articles %X Signal transduction ATPases with numerous domains (STAND) get activated through inducer-dependent assembly into multimeric platforms. This switch relies on the conversion of their nucleotide-binding oligomerization domain (NOD) from a closed, ADP-bound form to an open, ATP-bound form. The NOD closed form is stabilized by contacts with the arm, a domain that connects the NOD to the inducer-binding domain called the sensor. How the inducer triggers NOD opening remains unclear. Here, I pinpointed the NOD-arm interface of the MalT STAND transcription factor, and I generated a MalT variant in which this interface can be covalently locked on demand , thereby trapping the NOD in the closed state. By characterizing this locked variant, I found that the inducer is recognized in two steps: it first binds to the sole sensor with low affinity, which then triggers the recruitment of the arm to form a high-affinity arm-sensor inducer-binding site. Strikingly, this high-affinity binding step was incompatible with arm-NOD contacts maintaining the NOD closed. Through this toggling between two mutually exclusive states reminiscent of a single-pole double-throw switch, the arm couples inducer binding to NOD opening, shown here to precede nucleotide exchange. This scenario likely holds for other STANDs like mammalian NLR innate immunity receptors. %G English %2 https://pasteur.hal.science/pasteur-01160453/document %2 https://pasteur.hal.science/pasteur-01160453/file/Danot%202015.pdf %L pasteur-01160453 %U https://pasteur.hal.science/pasteur-01160453 %~ PASTEUR %~ CNRS %~ RIIP_PARIS %~ ANR