Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We show that MalT, the transcriptional activator of the Escherichia coli maltose regulon, specifically binds ATP and dATP with a high affinity (Kd = 0.4 microM) and exhibits a weak ATPase activity. Using an abortive initiation assay, we further show that activation of open complex formation by MalT depends on the presence of ATP in addition to that of maltotriose, the inducer of the maltose system. Similar experiments in which ATP was replaced by ADP or AMP-PNP, a non-hydrolysable analogue of ATP, demonstrate that this reaction does not require ATP hydrolysis. As revealed by DNase I footprinting, both ATP and maltotriose are required for the binding of the MalT protein to the mal promoter DNA.
 ...
PMID:MalT, the regulatory protein of the Escherichia coli maltose system, is an ATP-dependent transcriptional activator. 252 84

MalT, the transcriptional activator of the Escherichia coli maltose regulon, binds the MalT-dependent promoters and activates transcription initiation only in the presence of maltotriose and ATP (or adenylyl imidodiphosphate (AMP-PNP)). Cooperative binding of MalT to the array of cognate sites present in the MalT-dependent promoters suggests that promoter binding involves MalT oligomerization. Gel filtration and sedimentation experiments were used to analyze the quaternary structure of MalT in solution in the absence or presence of maltotriose and/or AMP-PNP, ATP, or ADP. The protein is monomeric in the absence of ligands and in the presence of ADP. In the presence of maltotriose, AMP-PNP, or ATP only, the protein self-associates, but a large fraction of the protein remains monomeric. In the presence of both maltotriose and AMP-PNP (ATP or ADP), the protein is essentially oligomeric, with the difference being that the oligomerization is less favored in the presence of ADP + maltotriose than in the presence of AMP-PNP + maltotriose. We present evidence that the association pathway comprises the following steps: monomers --> dimers --> (MalT)(n) --> aggregates, where 3 </= n </= 6. From these data, we conclude that the role of maltotriose and ATP as positive effectors is to induce the multimerization of MalT, and hence its cooperative binding to the mal promoters.
 ...
PMID:Self-association of the Escherichia coli transcription activator MalT in the presence of maltotriose and ATP. 1055 95

MalT, the dedicated transcriptional activator of the maltose regulon in Escherichia coli, is the prototype for a family of large (approximately 100 kDa) transcriptional activators. MalT self-association plays a key role in recognition of the target promoters, which contain several MalT sites that are cooperatively bound by the activator. The unliganded form of MalT is monomeric. The protein self-associates only in the presence of both ATP (or AMP-PNP, a non-hydrolysable analog of ATP) and maltotriose, the inducer. Here, we report cryo-electron microscopy analyses of MalT multimeric forms. We show that, in the presence of maltotriose and AMP-PNP, MalT associates into novel, polydisperse, curved homopolymers. The building block, corresponding to a MalT monomer, comprises an outer globular domain connected by a peduncle to an inner domain that mediates self-association. Image analyses highlight the significant conformational flexibility of these polymeric forms. In the presence of a DNA fragment containing a MalT-controlled promoter, malPp500, MalT forms homopolymers with a much smaller radius of curvature and a different conformation. We propose that MalT binding to the target promoters involves the assembly of a MalT homo-oligomer that is governed by the array of MalT sites present.
 ...
PMID:Oligomeric assemblies of the Escherichia coli MalT transcriptional activator revealed by cryo-electron microscopy and image processing. 1549 3