Saurav Misra

Assistant Staff at CCF

Ph.D.
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Molecular basis of protein quality control

RESEARCH DESCRIPTION

We use biochemistry to investigate the structures and interactions of proteins involved in several distinct areas of cellular signaling. Our tools include X-ray crystallography and nuclear magnetic resonance, calorimetry, biochemical assays, and other methods.

The primary interest in our laboratory is how cells carry out protein quality control. We are particularly interested in quality control of proteins that are prone to aggregation or misfolding. Such proteins are disproportionately involved in neurological diseases, including Parkinson’s disease, Alzheimer’s disease and cystic fibrosis.

To deal with misfolded proteins, cells have specialized their protein degradation system, using ubiquitin to tag proteins bound for destruction by the proteasome. We study the structure and interactions of CHIP (carboxy terminus of Hsc-70 interacting protein), a ubiquitin ligase that is intimately associated with heat shock proteins and ubiquitinates many misfolding-prone proteins, including a-synuclein (involved in Parkinson’s disease) and the cystic fibrosis transmembrane receptor. CHIP may ameliorate the neurotoxic effects of its substrates by functioning to clear them. CHIP also acts on proteins involved in cardiovascular disease and diabetic cardiomyopathy.

We study how CHIP interacts with the heat-shock machinery, with its substrates, and with other proteins involved in ubiquitination.

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