05 Nov 2014

In the bank

CLS crystallography scientists celebrate 500 protein structures

SASKATOON – The Canadian Macromolecular Crystallography Facility (CMCF) has announced the successful solution of 500 protein structures using the Canadian Light Source. The 3-D structures of proteins can be determined using powerful synchrotron X-ray light, and these structure models are deposited in the Protein Data Bank – a worldwide repository describing and showcasing proteins and other biological macromolecules. Many of these structures have been critical to the publication of 286 peer-reviewed journal articles.

The first protein structure from the CLS was obtained in 2006 on the first CMCF beamline. In 2011, a second beamline was commissioned. Since then, the number of CMCF researchers has grown to about 75 principal investigators from across Canada along with their staff and students. Several scientists from the US, as well as important commercial clients, regularly use the facility either in person or remotely.

The excellent quality of researchers that make use of the CMCF is highlighted in several influential works published in high-impact journals such asNatureScience and Cell. Examples include an article that recently appeared in Science describing the structure of parkin, a protein that if mutated is responsible for some types of Parkinson’s disease1. Detailed knowledge of this structure provides a framework for enhancing healthy parkin activity therapeutically. An article exploring invasion of host cells by parasites that cause malaria also appeared in Science2. Understanding the structural features of the critical proteins involved in such processes is key to the development of effective treatments.

Nature article explored how the human body recognizes attacking viral RNA, while another made a determination of “hot spots” on ryanodine receptor proteins that, when abnormally mutated, are involved in cardiac disease3,4. DNA methylation is intricately involved in cell development and affects everything from cell differentiation to the development of cancer. An article in Cell reported the mechanism by which specific proteins regulate DNA methylation and control target gene expression5. Such studies give researchers detailed structural information critical to our understanding of life, disease processes and, ultimately, our desire to improve the human condition.
                                                                                                         
This year marks another milestone because the Protein Data Bank has now surpassed 100,000 structure entries from human, animal, plant, bacterial and viral proteins as well as nucleic acids. Over 90,000 of these structures are the result of crystallography experiments. The results from investigators using the CMCF represent a significant contribution to this important pool of knowledge that scientists use to better understand biology, environmental processes, human health, disease, and develop new pharmaceuticals.

This important CLS achievement also occurs during the UNESCO International Year of Crystallography. It is the result of the hard work and dedication of CMCF users, CLS staff, and the CMCF beamline advisory team, consisting of crystallographers representing different regions of the country, currently including: Mirek Cygler (University of Saskatchewan, Chair), Albert Berghuis (McGill), Michel Fodje (CLS/U of S), Marie Fraser (University of Calgary), Mark Glover (University of Alberta), Pawel Grochulski (CLS/U of S), Brian Mark (University of Manitoba), Stanley Moore (U of S), Emil Pai (University of Toronto), James Rini (U of T), Joe Schrag (National Research Council), Natalie Strynadka (University of British Columbia) and Filip Van Petegem (UBC).

References:  1 Trempe et al., Science 340(6139), 1451-1455;  2 Tonkin et al., Science 333(6041), 463-467;  3 Abbas et al., Nature 494(7435), 60-64;  4 Tung et al., Nature 468(7323), 585-588;  5 Xu et al., Cell 151(6), 1200-1213.

Canadian Macromolecular Crystallography scientists: (back, l-r) Michel Fodje, Kathryn Janzen, Pawel Grochulski, (front, l-r) Shaun Labiuk and James Gorin designed, operate, maintain and develop the two CMCF beamlines used for crystallographic studies at the Canadian Light Source.
Crystal structure showing the interaction between proteins involved in host cell invasion by parasites that cause malaria. Understanding the structural features of such proteins is critical in the development of effective treatments. PDB 2Y8S

About the CLS:

The Canadian Light Source is Canada’s national centre for synchrotron research and a global centre of excellence in synchrotron science and its applications. Located on the University of Saskatchewan campus in Saskatoon, the CLS has hosted over 2,000 researchers from academic institutions, government, and industry from 10 provinces and 2 territories; delivered over 32,000 experimental shifts; received over 8,300 user visits; and provided a scientific service critical in over 1,000 scientific publications, since beginning operations in 2005.

CLS operations are funded by Canada Foundation for Innovation, Natural Sciences and Engineering Research Council, Western Economic Diversification Canada, National Research Council of Canada, Canadian Institutes of Health Research, the Government of Saskatchewan and the University of Saskatchewan.

Synchrotrons work by accelerating electrons in a tube to nearly the speed of light using powerful magnets and radio frequency waves. By manipulating the electrons, scientists can select different forms of very bright light using a spectrum of X-ray, infrared, and ultraviolet light to conduct experiments.

Synchrotrons are used to probe the structure of matter and analyze a host of physical, chemical, geological and biological processes. Information obtained by scientists can be used to help design new drugs, examine the structure of surfaces in order to develop more effective motor oils, build more powerful computer chips, develop new materials for safer medical implants, and help clean up mining wastes, to name a few applications.

For more information visit the CLS website 
For photos to accompany this story and more images from the CLS visit our Flickr gallery

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