The precise shapes of proteins at work inside our cells offer essential clues about the processes that drive health and disease. Structural biologists determine the forms of molecular machines, in atomic detail, to better understand how they function or what happens when they malfunction.
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SETD2 is a protein well known as a chromatin remodeler, one that helps turn genes on or off by modifying histone proteins in the nucleus of the cell. When researchers discovered that SETD2 is mutated or lost in several cancer types, most commonly a type of kidney cancer called clear-cell renal cell carcinoma, all eyes turned toward SETD2 function in the nucleus of the cell to explain these cancers.
In 2016, the lab of Dr. Cheryl Walker, director of the Center for Precision Environmental Health at Baylor College of Medicine, made the unexpected discovery that SETD2 not only remodels chromosomes in the nucleus, but also microtubules of the cytoskeleton outside the nucleus. The cytoskeleton is a dynamic network of interlinking protein thread-like structures, including filaments and microtubules that extend throughout the cell. It gives a cell its shape and internal organization and provides mechanical support that enables cells to carry out essential functions like division