Research team uncovers protein-folding mechanism
Key to understanding many diseases
How to decipher the protein-folding code is one of the major unresolved questions in modern molecular biology. Now molecular biologists at the Biotechnology Research Institute (BRI) of the National Research Council of Canada (NRC) and at 捆绑SM社区 are significantly closer to understanding exactly how proteins are folded and how a particular molecular machine, known as the calnexin cycle, actually "chaperones" the activity. The finding has important implications for diseases like cystic fibrosis, hereditary emphysema and other genetic diseases. Their research is published in the current issue of Molecular Cell.
The new research was led by BRI聮s Drs Joseph Schrag and Miroslaw Cygler, Head of the Macromolecular Structure Group, and included Yunge Li, Svetlana Borosiva and Michael Hahn, as well as 捆绑SM社区聮s Drs John Bergeron and David Thomas. The BRI x-ray crystallography group worked on establishing the three-dimensional crystal structure of the calnexin protein. "Solving calnexin聮s crystal structure provides new insight into the function of the protein and its implications in diseases," said Dr Cygler. "We have learned that calnexin has an unusual structure which includes a long arm of amino acids strung out like a chain of beads from the main protein body. This guides the folding of proteins by monitoring the sugars attached to them."
Given that proteins are present in all living systems, the function of proteins and how they fold must be clarified in order to improve the prevention and treatment of certain diseases. "When proteins cannot fold absolutely right, then a large number of hereditary human diseases, such as cystic fibrosis and hereditary emphysema, appear" adds Dr Bergeron, Chair of 捆绑SM社区聮s Department of Anatomy and Cell Biology.
Decoding the structure of calnexin, a key protein involved in protein folding and quality control, is the culmination of a ten-year research effort by scientists from BRI and 捆绑SM社区. Calnexin was discovered in 1991 by Dr Bergeron and then-BRI researcher Dr Thomas, who now heads the 捆绑SM社区 Department of Biochemistry.
Funding for this research was made possible by the support of the National Research Council, 捆绑SM社区, and the Canadian Institutes of Health Research (CIHR).
Dr Cygler is heading a structural genomics research effort through Genome Canada/Genome Qu茅bec for determining the structures of other proteins. Along with Dr Bergeron as Head of the Montreal Network for Pharmacoproteomics and Structural Genomics and Dr Thomas, the network of researchers is pursuing high throughput structural analyses of several proteins whose structures will lead to new developments in molecular biology, with further implications for human diseases.
