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Macromolecular Crystallography at the National Synchrotron Light Source

Robert M. Sweet, Ph.D.
P41RR012408
N/A
Retired

Center Overview

The Macromolecular Crystallography Research Resource (PXRR) provides facilities and support at the National Synchrotron Light Source for the benefit of outside and in-house investigators. The PXRR is supported by the NIH's National Center for Research Resources, and by the DOE Office of Biological and Environmental Research in its mission to create optimal facilities and environments for macromolecular structure determination by synchrotron X-ray diffraction. With a staff of about 18, the PXRR innovates new access modes such as Mail-in crystallography, builds new facilities, advances automation, develops remote participation software, collaborates with outside groups, teaches novice users, and supports visiting investigators with 7-day, 20-hours staff coverage.

Impact on Human Health

X-ray crystallography has transformed our understanding of biological processes. It was X-ray diffraction that provided the first clues to the structure of the DNA double helix nearly 60 years ago, giving profound insights into how DNA is replicated. One of the major driving forces in the continuing development of synchrotron radiation facilities worldwide has been the reality that knowledge of biological structure imparts deep insights into the mechanism of action of molecules and assemblies, and that the difficulty in determining those structures increases as they get larger.

Seven recent Nobel Prize winners in Chemistry depended on readily available synchrotron X-rays for their ground-breaking research: Sir John Walker of the MRC in 1997, Roderick MacKinnon of Rockefeller University in 2003, Roger Kornberg of Stanford University in 2006, Roger Tsien of Univ. Calif. San Diego in 2008, Venkatraman Ramakrishnan of the MRC, Thomas Steitz of Yale University, and Ada Yonath of the Weizman Institute of Science in 2009. The ribosome structures, honored with the 2009 Nobel Prize, are the largest with 150,000 atoms. Determination of this structure - the location of every atom! - was an amazing tour de force. These awards help prove the crucial role synchrotron radiation facilities play in our understanding of the mechanisms of life.

The routine use of synchrotron radiation for single crystal diffraction studies has revolutionized macromolecular structural biology. With the availability of brighter X-ray sources, the size and complexity of macromolecules that can be studied has increased by an order of magnitude, or three orders of magnitude in mass. On the other hand, the size of the crystals that can be produced almost always decreases as the complexity of the macromolecule increases. The advancements observed for the past 15 years in the development of cloning, expression, purification, and crystallization methods have been impressive. However, crystals of the most complex structures that are suitable for diffraction are often scarce and difficult to obtain. Therefore, continuing advances in synchrotron radiation sources, detectors, and software are required to tackle the most challenging problems, which are the ones most likely to make a significant impact on our knowledge of the functioning of living systems.