title: Crystal structure of the lambda repressor C-terminal domain provides a model for cooperative operator binding.
abstract: Interactions between transcription factors bound to separate operator sites commonly play an important role in gene regulation by mediating cooperative binding to the DNA. However, few detailed structural models for understanding the molecular basis of such cooperativity are available. The c1 repressor of bacteriophage lambda is a classic example of a protein that binds to its operator sites cooperatively. The C-terminal domain of the repressor mediates dimerization as well as a dimer-dimer interaction that results in the cooperative binding of two repressor dimers to adjacent operator sites. Here, we present the x-ray crystal structure of the lambda repressor C-terminal domain determined by multiwavelength anomalous diffraction. Remarkably, the interactions that mediate cooperativity are captured in the crystal, where two dimers associate about a 2-fold axis of symmetry. Based on the structure and previous genetic and biochemical data, we present a model for the cooperative binding of two lambda repressor dimers at adjacent operator sites.
authors.affiliation: The Johnson Foundation and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Bell
authors.forename: P
authors.initials: P
authors.lastname: Frescura
authors.forename: A
authors.initials: A
authors.lastname: Hochschild
authors.forename: M
authors.initials: M
authors.lastname: Lewis
mesh_terms: D000595:Amino Acid Sequence; D010582:Bacteriophage lambda; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins