Owen Zacarias
New York University
Chemical Biological Tools to Probe the Network of HspA2 Partners in Neurodegeneration
Heat-shock proteins (Hsps) comprise the cellular homeostasis machinery across various species. This machinery’s role in misfolded peptide refolding and degradation has been a subject of thorough investigation. The system comprises of an Hsp70, Hsp40, and a nucleotide exchange factor. In humans, the Hsp70 family of proteins consists of 8 canonical and 5 atypical isoforms. Furthermore, humans express over fifty Hsp40s, adding an additional layer of complexity to this machinery. In disease states like cancer and neurodegeneration, there has been evidence linked to the progression of the disease state and Hsp70 overexpression. In neurodegenerative diseases, the isoform HspA2 has been recently shown to be overexpressed. How HspA2 works in tandem with its Hsp40 counterparts is still largely unknown. HspA2, like other cytosolic Hsp70 isoforms, possess a C-terminal EEVD domain which is known to be crucial for binding partner Hsp40s. We aim to create a photo-crosslinking probe to assess which functional pairs of HspA2 are linked to its function and if we can tease out new partners that play a role in neurodegeneration.
Heat-shock proteins (Hsps) comprise the cellular homeostasis machinery across various species. This machinery’s role in misfolded peptide refolding and degradation has been a subject of thorough investigation. The system comprises of an Hsp70, Hsp40, and a nucleotide exchange factor. In humans, the Hsp70 family of proteins consists of 8 canonical and 5 atypical isoforms. Furthermore, humans express over fifty Hsp40s, adding an additional layer of complexity to this machinery. In disease states like cancer and neurodegeneration, there has been evidence linked to the progression of the disease state and Hsp70 overexpression. In neurodegenerative diseases, the isoform HspA2 has been recently shown to be overexpressed. How HspA2 works in tandem with its Hsp40 counterparts is still largely unknown. HspA2, like other cytosolic Hsp70 isoforms, possess a C-terminal EEVD domain which is known to be crucial for binding partner Hsp40s. We aim to create a photo-crosslinking probe to assess which functional pairs of HspA2 are linked to its function and if we can tease out new partners that play a role in neurodegeneration.