SwissFEL makes protein structures visible

Successful pilot experiment on biomolecules at the newest large research facility of PSI

For the development of new medicinal agents, accurate knowledge of biological processes in the body is a prerequisite. Here proteins play a crucial role. At the Paul Scherrer Institute PSI, the X-ray free-electron laser SwissFEL has now, for the first time, directed its strong light onto protein crystals and made their structures visible. The special characteristics of the X-ray laser enable completely novel experiments in which scientists can watch how proteins move and change their shape. The new method, which in Switzerland is only possible at PSI, will in the future aid in the discovery of new drugs.

Less than two years after the X-ray free-electron laser SwissFEL started operations, PSI researchers, together with the Swiss company leadXpro, have successfully completed their first experiment using it to study biological molecules. With that, they have achieved another milestone before this new PSI large research facility becomes available for experiments, at the beginning of 2019, to all users from academia and industry. SwissFEL is one of only five facilities worldwide in which researchers can investigate biological processes in proteins or protein complexes with high-energy X-ray laser light.

>Read more on the SwissFEL website

Image: Michael Hennig (left) and Karol Nass at the experiment station in SwissFEL where their pilot experiment was conducted.
Credit: Paul Scherrer Institute/Mahir Dzambegovic

First European XFEL research results published

High number of X-ray pulses per second reduces time needed for the study of biological structures.

Just days before the first anniversary of the start of European XFEL user operation, the first results based on research performed at the facility have been published. In the journal Nature Communications, the scientists, headed by Prof. Ilme Schlichting from Max-Planck-Institute for Medical Research in Heidelberg, Germany, together with colleagues from Rutgers State University of New Jersey, USA, France, DESY and European XFEL, describe their work using the intense X-ray laser beam to determine the 3D structure of several proteins. They demonstrate, for the first time that, under the conditions used at the time of the experiment an increased number of X-ray pulses per second as produced by the European XFEL can be successfully used to determine the structure of biomolecules. As much faster data collection is therefore possible, the time needed for an experiment could be significantly shortened. The detailed determination of the 3D structure of biomolecules is crucial for providing insights into informing the development of  novel drugs to treat diseases.

Prof. Ilme Schlichting said: “Our work shows that under the conditions used data can be collected at European XFEL at a rate much faster than has ever been previously possible. As the time and cost of experiments decrease, very soon many more researchers will be able to perform experiments at high repetition rate X-ray lasers. Our results are therefore of interest not only tor the fields of biology and medicine, but also physics, chemistry and other disciplines.”

>Read more on the European XFEL website

Image: Guest scientist Tokushi Sato working at the sample chamber of the SPB/SFX instrument.
Credit: European XFEL

ALS passes the 7000-protein milestone

The eight structural biology beamlines at the ALS have now collectively deposited over 7000 proteins into the Protein Data Bank (PDB), a worldwide, open-access repository of protein structures. The 7000th ALS protein structure (entry no. 6C7C) is an enzyme from Mycobacterium ulcerans (strain Agy99), solved with data from Beamline 5.0.2. This bacterium produces a toxin that eats away at skin tissue, causing what’s known as Buruli ulcers (Google at your own risk!). The bacterium is antibiotic-resistant, and treatment involves the surgical removal of infected tissues, including amputation.

The enzyme structure was solved by a group from the Seattle Structural Genomics Center for Infectious Disease (SSGID), whose mission is to obtain crystal structures of potential drug targets on the priority pathogen list of the National Institute of Allergy and Infectious Diseases (NIAID). As of May 2018, SSGCID has deposited 1090 structures in the PDB, with data for more than a quarter of those collected at ALS beamlines.

>Read more on the Advanced Light Source website

Image: PDB 6C7C: Enoyl-CoA hydratase, an enzyme from M. ulcerans (strain Agy99).

With help from a few friends

Researchers discover the precise make-up of a molecular chaperone complex

A complex made up of three proteins, Hsp90, Sgt1, and Rar1, is thought to stabilise an important immune protein known as nucleotide-binding domain and leucine-rich repeat containing protein. While the structure of the Sgt1-Hsp90-Rar1 protein is known, the stoichiometry of the complex has remained elusive. In a paper published in Frontiers in Molecular Biosciences, Dr Chrisostomos Prodromou of the University of Sussex and Dr Minghao Zhang of the University of Oxford worked with Professor Giuliano Siligardi at the Circular Dichroism beamline (B23) at Diamond Light Source to clarify the detailed make-up of the complex. Using synchrotron radiation circular dichroism, they revealed that it consists of an Hsp90 dimer, two Sgt1 molecules, and a single Rar1 molecule. The stoichiometry of the full complex potentially allows two NLR molecules to bind, a finding which may open avenues of research into how these proteins form dimers.

>Read more on the Diamond Light Source website

Figure: (extract) The structure of the Sgt1-Hsp90-Rar1 complex with an Hsp90 dimer, two Sgt1 molecules, and a single Rar1. Entire image here.

Crystallographers identify 1,000 protein structures

The Canadian Light Source is celebrating two milestones reached by scientists who have conducted research at the national facility at the University of Saskatchewan.

Scientists have solved 1,000 protein structures using data collected at CLS’s CMCF beamlines. These have been added to the Protein Data Bank – a collection of structures solved by researchers globally. Researchers have also published 500 scientific papers based on their work using the crystallography beamlines.

Proteins are the building blocks of life and are described as the body’s workhorses. The body is made of trillions of cells. Cells produce proteins, which do the work of breaking down food, sending messages to other cells, and fighting bacteria, viruses and parasites. The discoveries at the CLS range from how the malaria parasite invades red blood cells to why superbugs are resistant to certain antibiotics and how parkin protein mutations result in some types of Parkinson’s disease. Understanding how these and other such proteins work can potentially save millions of lives.

>Read more on the Canadian Light Source website

Image: PDB ID: 6B0S