How a very “sociable” protein can hold clues about Alzheimer’s origin

The origin of the most prevalent form of Alzheimer’s disease, which accounts for 95% of cases, is still not clear despite decades of scientific studies. “Before understanding the pathology, we need to understand the biology”, explains Montse Soler López, scientist leading research on Alzheimer’s disease at the ESRF. “The only thing we are sure about is that the most common form of Alzheimer’s is linked with ageing”, she asserts.

So researchers have been focusing on parts of the body that degrade dramatically with age. Neurons, for example, are long-lived cells, meaning that they don’t renew themselves like other cells do. Neurons lodge mitochondria, which are so-called the “powerhouse of cell” because of their active role generating energy in the body. With time, mitochondria suffer oxidative stress and this leads to their malfunction. It has been recently discovered that people with Alzheimer’s may have an accumulation of amyloids inside mitochondria (previously it was thought amyloids were only outside the neurons). Montse Soler López is trying to find whether there is a link between mitochondrial dysfunction, presence of amyloids and early disease symptoms. “We believe that malfunctioning of the mitochondria can take place 20 years before the person shows symptoms of the disease”.

Read more on the ESRF website

Newly discovered photosynthesis enzyme yields evolutionary clues

Rubisco is one of the oldest carbon-fixing enzymes on the planet, taking CO2 from the atmosphere and fixing it into sugar for plants and other photosynthetic organisms. Form I (“form one”) rubisco goes back nearly 2.4 billion years and is a key focus of scientists studying the evolution of life as well as those seeking to develop bio-based fuels and renewable-energy technologies. A newly discovered form of rubisco—dubbed form I′ (“one prime”)—is thought to represent a missing link in the evolution of photosynthetic organisms, potentially providing clues as to how this enzyme changed the planet.

To learn how form I′ rubisco compares to other rubisco enzymes, researchers performed x-ray crystallography at Advanced Light Source (ALS) Beamline 8.2.2. Then, to capture how the enzyme’s structure changes during different states of activity, they applied small-angle x-ray scattering (SAXS) using Beamline 12.3.1 (SIBYLS). This combination of approaches enables scientists to construct unprecedented models of complex molecules as they appear in nature.

Read more on the ALS website

Image: A ribbon diagram (left) and molecular surface representation (right) of carbon-fixing form I′ rubisco, showing eight molecular subunits without the small subunits found in other forms of rubisco. An x-ray diffraction pattern of the enzyme, also generated by the research team, is in the background.

Credit: Henrique Pereira/Berkeley Lab

“foot-2-foot” interaction sheds light on bacterial conjugation

Bacteria possess mechanisms to establish communication between cells. This is especially important in bacterial conjugation, a process that allows bacteria to share genetic material. This is often used by bacteria to transfer antibiotic resistance genes and other virulence factors to neighbor cells, increasing the antibiotic resistance spread.

Now, a research team of ALBA scientists report the structural mechanism by which two proteins, Rap and Rco, act together to regulate conjugation. Rco is a repressor of conjugation, whereas Rap binds Rco and prevents Rco-mediated conjugation repression, thus resulting in an activation of the conjugation mechanism. The main results of the study show that Rap contains a binding pocket were a short peptide can bind, producing structural changes in Rap that forces its tetramerization, releasing Rco for blocking conjugation. Tetramerization occurs through an interaction that scientists named “foot-2-foot”, which differs significantly from the model proposed for other proteins of the Rap family.

Read more on the ALBA website

Image: RappLS20 tetramerization, side view of the peptide-bound tetramer. The red arrows indicate the loops connecting helices H4 and H5. (C) Zoom of the area around the N-terminus of helix H4, showing the insertion of this helix into the opposite monomer. The homotetramerization caused by the foot-2-foot interactions of the NTDs of RappLS20 provides an explanation for the activation of the RcopLS20 partner. In the absence of the peptide, the NTDs are positioned such that they allow the interaction with RcopLS20. However, upon binding the signaling peptide, the NTDs shift outwards, facilitating the formation of the homotetramer, leading to a change of the interaction surface of the NTDs that is no longer available for interactions with RcopLS20

Measuring interfaces in 3D printing

3D printing (3DP) leads to many defects and interfaces within printed parts. Failure during performance in the road-to-road and layer-by-layer processed parts appears at these interfaces and defects. Understanding the root cause of these limitations is key. 

Only by mapping the sample via µ-beam SAX was it possible to determine the source of a peculiar defect and interface morphology. To the surprise of the scientists the alignment of nanoparticles is not uniform and not random within roads and layers of an epoxy carbon fiber reinforced composite and explains some of the achieved mechanical properties and microscopy results.

Read more on the Cornell High Energy Synchrotron Source (CHESS) website

Image: 3D printing degree of orientation

Credit: CHESS

Bone breakages and hip fracture risk is linked to nanoscale bone inflexibility

Experiments carried out at Diamond using high energy intense beams of X-rays examined bone flexibility at the nanoscale. This allowed scientists to assess how collagen and minerals within bone flex and then break apart under load – in the nanostructure of hip bone samples.  

The report’s findings suggest that doctors should look not only at bone density, but also bone flexibility, when deciding how to prevent bone breakages. 

New research undertaken at Diamond’s Small Angle X-ray Scattering beamline (I22) has highlighted a gap in preventative treatment in patients prone to bone fractures.  The study, published in Scientific Reports and led by Imperial College London, found that flexibility as well as density in the bone nanostructure is an important factor in assessing how likely someone is to suffer fractures. 

Read more on the Diamond website

Image: Nanostructure: Collagen and mineral strain under load. Image: Shaocheng Ma, Imperial College London.

Significant progress on ultraflexible solar cells

Research from Monash University, the University of Tokyo and RIKEN, partly undertaken at the Australian Synchrotron, has produced an ultra-flexible ultra-thin organic solar cell that delivered a world-leading performance under significant stretching and strain.

The development paves the way forward for a new class of stretchable and bendable solar cells in wearable devices, such as fitness and health trackers, and smart watches with complex curved surfaces.

The advance, which was published in Joule, was made possible by designing an ultra-thin material based on a blend of polymer, fullerene and non-fullerene molecules with the desired mechanical properties and power efficiency, according to Dr Wenchao Huang, a Research Fellow at Monash University and the article’s first author.
The thickness of the solar cell film is only three micrometres, which is ten times smaller than the width of a human hair.

Dr Huang, who completed his PhD in the lab of Prof Chris McNeill at Monash on flexible organic solar cells, received the Australian Synchrotron’s Stephen Wilkins Medal in 2016 for his exceptional doctoral thesis that made use of the synchrotron-based research capabilities at the facility.

>Read more no the Autralian Lightsource at ANSTO website

Image: Schematic of ultraflexible solar cell

Assembly lines for designer bioactive compounds

Researchers successfully bioengineered changes to a molecular “assembly line” for bioactive compounds, based in part on insights gained from small-angle x-ray scattering at the Advanced Light Source (ALS).

The ability to re-engineer these assembly lines could improve their performance and facilitate the synthesis of new medically useful compounds.

Microbes are known to possess molecular “assembly lines” that produce an important class of compounds, many of which have uses as antibiotics, antifungals, and immunosuppressants. The compounds are peptides—chains of amino acids like RNA, but shorter and produced, not by ribosomes, but by cellular machines known as nonribosomal peptide synthetases (NRPSs).

>Read more on the Advanced Light Source website

Image: Top: Comparison of experimental SAXS scattering data (black) with theoretical curves (green) obtained using an ensemble optimization method (EOM) shows excellent agreement. Bottom: LgrA structural models corresponding to the EOM analyses show large differences in conformation, similar to the differences observed using crystallography.