Cells respond to various proteotoxic stimuli and maintain protein homeostasis through a conserved mechanism called the heat-shock response, which is characterized by the enhanced synthesis of heat-shock proteins. This response is mediated by heat-shock factors (HSFs). Four genes encoding HSF1–HSF4 exist in the genome of mammals. In this protein family, HSF1 is the orthologue of the single HSF in lower eukaryotic organisms and is the major regulator of the heat-shock response, while HSF2, which shows low sequence homology to HSF1, serves as a developmental regulator. Increasing evidence has revealed biochemical properties and functional roles that are unique to HSF2, such as its DNA-binding preference and sumoylation patterns, which are distinct from those of HSF1. The structural basis for such differences, however, is poorly understood owing to the lack of available mammalian HSF structures. The N-terminal DNA-binding domain (DBD) is the most conserved functional module and is the only crystallizable domain in HSFs. To date, only HSF1 homologue structures from yeast and fruit fly have been determined. Along with extensive studies of the HSF family, more structural information, particularly from members with a remoter phylogenic relationship to the reported structures,e.g.HSF2, is needed in order to better understand the detailed mechanisms of HSF biology. In this work, the recombinant DBD (residues 7–112) from human HSF2 was produced inEscherichia coliand crystallized. An X-ray diffraction data set was collected to 1.32 Å resolution from a crystal belonging to space groupP212121with unit cell-parametersa= 65.66,b= 67.26,c= 93.25 Å. The data-evaluation statistics revealed good quality of the collected data, thus establishing a solid basis for the determination of the first structure at atomic resolution in this protein family.
Disarming Bacterial Virulence through Chemical Inhibition of the DNA Binding Domain of an AraC-like Transcriptional Activator Protein
