Protein crystallography – Lightsources.org

50th Anniversary of the SSRL synchrotron radiation & protein crystallography initiative

2025/12/102025/12/12

Synchrotron-based protein crystallography continues to accelerate, driven by new and upgraded high-brightness sources, improved optics, faster large-area detectors, robust automation and streamlined data handling. These advances are making increasingly challenging structural biology projects feasible and are reshaping how synchrotron experiments integrate with today’s wider structural biology methods. While AI models are now routinely used in molecular replacement software for macromolecular crystal structure determination, synchrotron experimental methods remain vital for detailed model refinement, and even validating AI models. Also extracting key chemical information, with anomalous dispersion at tuneable beamlines still playing an important role especially in identifying metals and other such atoms in proteins.

This special issue in Journal of Synchrotron Radiation, edited by John R. Helliwell and Marian Szebenyi, and their Overview with Colin Nave, with a Perspective from Keith Hodgson, as well as articles from a majority of the facilities worldwide, explores the evolving landscape in depth. It also highlights the expanding impact of fragment screening and binding studies (from cryogenic up to body temperatures) and the rapidly developing frontiers of time-resolved and serial crystallography. In particular, the issue charts the synergy between XFEL-based serial femtosecond crystallography and serial synchrotron crystallography, culminating in recent demonstrations of microsecond time resolution at upgraded synchrotrons such as ESRF–EBS, pointing to a future where synchrotrons and X-ray lasers together enable ever more powerful studies of biological structure, dynamics and function.

Access the special issue here

Image Credit:

Phillips, J.C., Wlodawer, A., Yevitz, M.M. and Hodgson, K.O., 1976. Applications of synchrotron radiation to protein crystallography: preliminary results. Proceedings of the National Academy of Sciences, 73(1), pp.128-132.

Rosenbaum, G., Holmes, K.C. and Witz, J., 1971. Synchrotron radiation as a source for X-ray diffraction. Nature, 230(5294), pp.434-437.

Sharks Shed Light on Origins of Adaptive Immune System

2025/08/262025/09/11

The Advanced Light Source (ALS) characterized a protein from a modern shark gene that explains the evolution of the adaptive immune system shared by all vertebrates.

Understanding the emergence of the adaptive immune system may aid researchers in advancing immunology, genetics, and biotechnology.

Left: The crystallographic model of the N-terminus of the UrIg2 protein from a nurse shark. Right: An example of one modern human antibody (IgG) whose variable region gene undergoes rearrangement.

The rise of adaptive immunity

Humans defend against infections through both the innate and adaptive immune systems. The innate response provides the first line of rapid defense, but it lacks both a way to address specific pathogens and a memory response to launch against attack by a returning invader. The adaptive immune system acts as a second line of defense. It lags behind the innate system because it must construct the antibodies to fight specific pathogens. The strength of this dual approach lies in the memory retained in the cells that produce antibodies that can be recalled to neutralize a returning threat.

The adaptive immune system is shared by all vertebrates and is believed to have developed soon after a genome-wide duplication event that occurred approximately 500 million years ago. The scientific community theorizes that the adaptive immune system developed when a mobile genetic element from a microbe—a recombination-activating gene (RAG) transposon—inserted itself into and split a gene in a eukaryotic cell, likely a white blood cell.

This random event led to a monumental and life-altering outcome. The process brought the repetitive elements from the transposon into this fractured gene with the RAG enzymes, which sparked the generation of an incalculable number of new proteins. To repair the fracture, the cell called in specialized machinery—double strand break repair enzymes—to fix the broken strands of genetic material. Proteins encoded by such “rearranged” genes eventually became antibodies—the front line of defense in the adaptive immune response.

Read more on ALS website

#SynchroLightAt75 – From the Ribosome to CRISPR

2022/10/112022/10/12

Structural Biology at the ALS: From the Ribosome to CRISPR

Since the first protein crystallography beamline came online here in 1997, thousands of protein structures have been solved at the Advanced Light Source (ALS). One of the earliest high-profile structures was that of the full ribosome complex, where all the proteins necessary for life are produced based on RNA blueprints. The results reinforced the impression that the ribosome is a dynamic molecular machine with moving parts and a very complicated mechanism of action. More recently, the ALS has contributed to a greater understanding of programmable CRISPR proteins such as Cas9. In contrast to earlier genome-editing tools, Cas9 transforms the complicated and expensive process of gene editing into something simpler and more routine, like applying a genetic plug-in. In 2020, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for “the development of a method for genome editing.”