title: Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family.
abstract: The Lrp/AsnC family of transcriptional regulatory proteins is found in both archaea and bacteria. Members of the family influence cellular metabolism in both a global (Lrp) and specific (AsnC) manner, often in response to exogenous amino acid effectors. In the present study we have determined both the first bacterial and the highest resolution structures for members of the family. Escherichia coli AsnC is a specific gene regulator whose activity is triggered by asparagine binding. Bacillus subtilis LrpC is a global regulator involved in chromosome condensation. Our AsnC-asparagine structure is the first for a regulator-effector complex and is revealed as an octameric disc. Key ligand recognition residues are identified together with a route for ligand access. The LrpC structure reveals a stable octamer supportive of a topological role in dynamic DNA packaging. The structures yield significant clues to the functionality of Lrp/AsnC-type regulators with respect to ligand binding and oligomerization states as well as to their role in specific and global DNA regulation.
authors.affiliation: Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Thaw
authors.forename: Svetlana E
authors.initials: SE
authors.lastname: Sedelnikova
authors.forename: Tatyana
authors.initials: T
authors.lastname: Muranova
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wiese
authors.forename: Sylvia
authors.initials: S
authors.lastname: Ayora
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alonso
authors.forename: Arie B
authors.initials: AB
authors.lastname: Brinkman
authors.forename: Jasper
authors.initials: J
authors.lastname: Akerboom
authors.forename: John
authors.initials: J
authors.lastname: van der Oost
authors.forename: John B
authors.initials: JB
authors.lastname: Rafferty
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism; D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C509334:AsnC protein, E coli; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008024:Ligands; D015534:Trans-Activators; D014157:Transcription Factors; D001216:Asparagine