Tuesday, November 24, 2009
Nogales Lab Research
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,
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.