The Nogales Lab

Monday, May 12, 2008

The SWI/SNF family of chromatin remodeling complexes uses ATP hydrolysis to modify the structure of nucleosomes in order to allow access of DNA-interacting proteins to their target sequences. Two closely related human chromatin remodeling factors, PBAF promotion SWI/SNF-A and SWI/SNF-B (or P-BAF) were identified and purified in the Tjian lab (Lemon et al., 2001). We have determined the structure of the human PBAF by single particle analysis of negatively stained samples (Leschziner et al., Structure 2005). The complex contains a larger density to which two smaller knobs are attached, surrounding a central cavity. One of these knobs appears remarkably flexible. Using two-dimensional image analysis we have mapped the nucleosome-binding site to the central cavity in contact with the flexible knob. Thus, the flexibility of this region might be biologically relevant during the remodeling cycle. We are now studying a number of closely related human, fly, and yeast complexes in collaboration with the labs of Robert Tjian and Brad Cairns (University of Utah), with the goal of understanding the general mechanism of nucleosome remodeling and the specific properties of each complex.