An international team led by researchers at the University of Toronto and the Broad Institute of MIT and Harvard has assembled the first large-scale, publicly available map to show the impact of mutations on where proteins end up in the cell. The team developed a high-throughput imaging platform to assess the influence of nearly 3,500 mutations on protein location. They found that roughly one in six disease-causing mutations led to proteins ending up in the wrong location in the cell.
"Technological advances in genetic sequencing have allowed researchers to identify thousands of protein mutations that cause disease," said Jessica Lacoste, co-lead author on the study and postdoctoral fellow at U of T's Donnelly Center for Cellular and Biomolecular Research. "We are now able to identify these mutations in patients at the clinic, but we have no idea what their consequences are for cellular processes. This study was meant to help bridge that gap in knowledge.
" The study was published recently in the journal Cell . There are several ways genetic mutations can affect proteins produced in the cell. For example, they can reduce their overall stability by impairing their ability to fold, alter their interactions with other proteins or disrupt their movement to various regions of the cell.
While the first two effects have been fairly well-studied, much less is known about the third. Improving our understanding of the impact of mutations on protein localization is essential to elucidati.
