Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1

An organism’s DNA contains thousands of genes, not all of which are active at the same time. Cells use a number of methods to carefully control when particular genes are switched on or off. For example, proteins called transcription factors can activate a gene by binding to particular regions of DNA called promoters. One such transcription factor is called the TATA-binding protein (TBP for short). Mot1 is a remodeling enzyme that can form a “complex” with TBP by binding to it, and in doing so remove TBP from DNA. This silences the genes at those sites. The freed TBP can then bind to other promoters that lack Mot1 and activate the genes found there. In 2011, researchers revealed the structure of the complex formed between TBP and Mot1 after TBP has been detached from DNA. However, the structure of the complex that forms while TBP is still bound to the DNA molecule was not known. Butryn et al. – including several of the researchers involved in the 2011 work – have now described the structure of this complex using X-ray crystallography and electron microscopy. Another protein called negative cofactor 2 is also part of the complex, and helps to stabilize it. Butryn et al. found that Mot1 reduces the strength of the interactions between DNA and both TBP and negative cofactor 2. Binding to TBP and negative cofactor 2 causes the DNA molecule to bend; however, if Mot1 is also in the complex, the DNA becomes less bent. By making these changes, Mot1 is likely to prime TBP to detach from the DNA. Since the current structures do not yet reveal the atomic structure of Mot1’s ATP dependent DNA motor domain, the next challenge is to visualize the entire complex at atomic resolution.