Scientists develop strategy to engineer artificial allosteric sites in protein complexes

According to a recently published research paper by a team of scientists, a groundbreaking approach has been developed to create artificial allosteric sites (where by binding an effector molecule, activity at the distal active site is regulated) in protein complexes. This breakthrough research holds significant promise for a wide range of applications in industrial, biological, medical, and agricultural fields.

The team’s work is published in Nature Chemistry on 06 July 2023 at 16:00 (London time).


Protein complexes, such as hemoglobin and molecular motors, exert concerted functions through cooperative work between the subunits (constituent proteins in the protein complex). This orchestration is enabled by the allosteric mechanism. The allosteric effect, regulation of function at an active site in a subunit by the binding of an effector molecule to an allosteric site in another subunit, was originally proposed in the 1960s and since then it has remained one of the most important topics in the biochemistry field. The research team developed a strategy for designing artificial allosteric sites into protein complexes to regulate a concerted function of a protein complex. “The creation of artificial allosteric sites into protein complexes has the potential to reveal fundamental principles for allostery and serve as tools for synthetic biology,” said Nobuyasu Koga, a professor at the Osaka University.


The research team hypothesized that allosteric sites in protein complexes can be created by restoring lost functions of the pseudo-active sites which are predicted to have been lost during evolution. Various protein complexes include subunits that have pseudo-active sites. It has been
reported that pseudo-active sites have an allosteric connection with active sites in other subunits. For example, a pseudo-active site in a subunit, which has lost ATPase activity but still exhibits ATP-binding ability, activates another subunit’s active site upon binding to ATP. (At the cellular
level, ATP is the source of energy. ATPase describes the enzyme’s ability to decompose ATP.) Such studies support the idea that distinct allosteric sites can be created into protein complexes by engineering pseudo-active sites.

Read more on the Photon Factory website

Image: Fig. 1 Design of allosteric sites into a rotary molecular motor

#SynchroLightAt75 – Photon Factory at the dawn of structural biology using SR

The Photon Factory opened its first dedicated protein crystallography beamline with a Weissenberg camera in the mid-1980s. Prof. Ada Yonath, who was awarded the Nobel Prize in Chemistry in 2009 for her work on the structure-function analysis of ribosomes, was working at the Photon Factory at this time. The cryo-crystallography developed at the time led to the successful structural analysis.

Read more about the 2009 Nobel Prize in Chemistry and KEK’s Photon Factory here: KEK feature article

Image: Cryo-cooling system developed by Prof. Ada Yonath installed at the Photon Factory

Credit: Photo courtesy of Prof. Noriyoshi Sakabe

#SynchroLightAt75 – Development of the first in-vacuum undulator in the world

The development of in-vacuum undulators, in which a short period is achieved by placing periodic magnet inside the accelerator’s vacuum pipe, began at KEK around 1988, and light was successfully generated for the first time in December 1990.

This technology can transform synchrotron radiation facilities into compact and energy-saving ones, because short-period undulators can generate high energy and intense X-rays even in 3-GeV class storage ring. The development has led to a trend towards the construction of synchrotron radiation facilities installed in-vacuum undulators around the world.

To read more #SychroLightAt75 highlights, visit Highlights – Lightsources.org

Image: The first in-vacuum undulator (period length : 4cm)

Credit: Photon Factory, KEK

Hybrid Ring – Conceptual design of light source that allows simultaneous use of two beams

A new idea for epochal synchrotron radiation facility is proposed at the Photon Factory jointly operated by the Institute of Materials Structure Science and the Accelerator Laboratory of the High Energy Accelerator Research Organization (KEK). The new facility called the Hybrid Ring is the advanced storage ring light source combined with a long pulsed superconducting linear accelerator.

The Photon Factory (PF) was the first dedicated synchrotron radiation facility in Japan with a wide range of photon energy from VSX to X-rays. From its first beam in 1982, PF widely supports both basic science and its application of the researchers from universities, national organizations, and private companies. Now, KEK aims to construct a successor facility to the Photon Factory by the early 2030s that is the 50th anniversary of the first beam. New design for the light source facility suitable for a world-class accelerator research institute is underway.

A research group led by Associate Professor Kentaro Harada and Professor Yukinori Kobayashi at the Accelerator Division 6 of the Accelerator Laboratory and Professor Nobumasa Funamori at the Photon Factory of the Institute of Materials Structure Science have developed a new concept of a synchrotron radiation facility called the Hybrid Ring. The Hybrid Ring can not only promote conventional synchrotron radiation user experiments but also develop a new type of user experiment by simultaneous use of two synchrotron radiation beams. These features are expected to make further contributions to a wider range of scientific and technological fields.

Read more on the KEK website

Image:  Conceptual diagram of the Hybrid Ring

A very powerful method that illuminates all research fields

Photon Factory at KEK – #LightSourceSelfie

Science is ever-evolving. This is particularly true in the world of light sources. As science, technology and computing advances are made, the machines that enable all the amazing scientific research advance too.

Kentaro Harada is an Associate Professor in the Beam dynamics and Magnets Group at KEK’s Photon Factory in Japan. As an accelerator scientist, his research is centred around magnets, power supplies, beam diagnostics and the operation of accelerators. The goals of Kentaro and his colleagues are to improve present accelerators and to design accelerators that will drive the science of the future. In his insightful #LightSourceSelfie, Kentaro says, “I think research and engineering are like the arts. The expression of uniqueness is first motivation. My goal is to do what only I can do.”

Photon Factory Highlights 2020

The research highlights based on the Photon Factory (PF) users’ program during fiscal 2020 (April 2020 – March 2021), is now available on the web.

The sections covered include:

Materials Science

Chemical Science

Earth & Planetary Science

Life Science

Instrumentation & Techniques

Accelerator

Access these highlights via the Photon Factory website

Image: Highlights 2020 cover

Credit: Photon Factory, KEK

Analysing asteroid Ryugu samples

The asteroid Ryugu samples brought back by JAXA’s asteroid explorer “Hayabusa2” in December 2020 are analyzed by six initial analysis teams for one year from June 2021. Among the initial analysis teams, the “Stone Material Analysis Team” and the “Organic Macromolecule Analysis Team” conducts their analysis at the Photon Factory, KEK.

It is thought that asteroids such as Ryugu may have brought water and organic matter to the Earth in the past. By integrating the results of each team’s analysis, we will be closer to solving the great mystery of how life came to be on the Earth.

Read more on the HAYABUSA2-IMSS website

Image : Primordial solar system. 

Exploring the scale of meteorite impact from minerals

Laboratory-based shock experiments on minerals

Key Points
– Shock experiments were performed on baddeleyite (a zirconia mineral) in a laboratory, during which time its crystal structure dynamics were observed directly using a synchrotron X-ray.
– The crystal structure changed upon compression before returning to its original state when released.
– Geologists can use this information to estimate the scale of a past impact event using baddeleyite present in rocks.

Collisions of celestial bodies have formed and affected the evolution of planets. One well-known hypothesis is that an asteroid impact caused the mass extinction of dinosaurs on Earth ~65 million years ago. Understanding the scale of an impact event is essential to studying the evolution of a similar planet. Impact events cause shock metamorphism in rocks and minerals in the crust of a planet (see Fig. 1), and shock metamorphosed minerals can be used to identify and date impact events and as barometric indicators. Baddeleyite (ZrO2) is one mineral that can be used as a shock-pressure barometer. The mineral is widespread on Earth, the Moon, Mars, and meteorites; it is also known to show traits of shock
metamorphism.

Read more on the KEK (Photon Factory) website

Image: Meteorite impact produces shock compressions in rocks. Source: KEK (Photon Factory)

Every moment of ultrafast chemical bonding now captured on film

The emerging moment of bond formation, two separate bonding steps, and subsequent vibrational motions were visualized.

Targeted cancer drugs work by striking a tight bond between cancer cell and specific molecular targets that are involved in the growth and spread of cancer. Detailed images of such chemical bonding sites or pathways can provide key information necessary for maximizing the efficacy of oncogene treatments. However, atomic movements in a molecule
have never been captured in the middle of the action, not even for an extremely simple molecule such as a triatomic molecule, made of only three atoms. A research team led by IHEE Hyotcherl of the Institute for Basic Science (IBS, South Korea) (Professor, Department of Chemistry, KAIST), in collaboration with scientists at the Institute of Materials Structure Science of KEK (KEK IMSS, Japan), RIKEN (Japan) and Pohang Accelerator Laboratory (PAL, South Korea), reported the direct observation of the birthing moment of chemical bonds by tracking real-time atomic positions in the molecule. “We finally succeeded in capturing the ongoing reaction process of the chemical bond formation in the gold trimer. The femtosecond-resolution images revealed that such molecular events
took place in two separate stages, not simultaneously as previously assumed,” says Associate Director IHEE Hyotcherl, the corresponding author of the study. “The atoms in the gold trimer complex atoms remain in motion even after the chemical bonding is complete. The
distance between the atoms increased and decreased periodically, exhibiting the molecular vibration. These visualized molecular vibrations allowed us to name the characteristic motion of each observed vibrational mode.” adds Ihee.

>Read more on the KEK (Photon Factory) website

Image: Figure 2. (left) Time-dependent positions of the wave packet in the multidimensional nuclear coordinates were obtained from the femtosecond x-ray scattering experiment on a gold trimer complex. (Credit: Nature & IBS) (right) By inspecting the motion of the wave packet, it was revealed that the bond formation reaction in the gold trimer complex occurs through an asynchronous bond formation mechanism. (Yellow: gold atoms, gray: carbon atom, blue: nitrogen atom, 1000 times 1 fs is 1 picosecond (ps), 1000 times 1 ps is 1 nanosecond (ns))

Credit: KEK IMSS

Lab. Tour of KEK during international workshop

International Joint symposium of 3rd Innovative Measurement and Analysis for Structural Materials and TIA-Fraunhofer workshop

The conference was held at AIST from Oct.3 to Oct.6, 2017. This conference has been held as an annual meeting of Innovative Measurement and Analysis (TIA) Group in a national project: the Structural Materials for Innovation of the Cross ministerial Strategic Innovation Promotion Program (SIP) of Japan Science and Technology (JST). Researchers including ones from Fraunhofer Institute and University of Bristol, gave presentations and discussed their mutual interests in the field of advanced analytical techniques, non-destructive inspection, CFRP (carbon-reinforced plastic), and ceramic coating.

Prof. Yoshitaka Kimura received the Order of the Sacred Treasure

A disctinction for his long term contribution in the field of education and research activities

In the fall of 2016, Dr. Yoshitaka Kimura, Professor Emeritus of KEK, received the Order of the Sacred Treasure, Gold Rays with Neck Ribbon, from Japanese Government for his long term contribution in the field of education and research activities.

In 1966, he received a Ph.D. at University of Tokyo, and started his career as Research Associate, School of Science, at University of Tokyo. From 1967 to 1968, he developed experimental facilities for nuclear physics using cryogenics and superconductive technologies as Lecturer, School of Engineering. During 1970 and 1971, Dr. Kimura was engaged in the high energy physics experiments with Proton Synchrotron at CERN.

When National Laboratory for High Energy Physics (KEK), the predecessor of High Energy Accelerator Research Organization (KEK), was established in 1971, he came to KEK as Associate Professor. Then he joined design and construction of KEK‘s 12 GeV Proton Synchrotron (KEK-PS). Above all in the machine design, construction of beam transport system, and beam development studies, he played leading role and led KEK-PS to success.

A better quality of tomography images

A research group composed of Dr. Naoki Sunaguchi (Gunma University), Prof. Tetsuya Yuasa (Yamagata University), M.D. Rajiv Gupta (Massachusetts General Hospital), Shin-ichi Hirano (Mercian Cleantec Corporation, MiZ Company Limited), and Prof. Masami Ando (Tokyo University of Science and Emeritus Professor at KEK) developed a new algorithm to improve the quality of an X-ray phase-contrast image.

X-ray phase-contrast imaging can provide far higher contrast in soft tissue compared to classical absorption-based imaging. Many groups have been developing a variety of imaging methods for potential clinical use. All these imaging methods suffer from a common problem: severe imaging artefacts arise when x-ray phase alternation exceeds the dynamic range of the imaging system, typically in the vicinity of bones and dense calcifications. These artefacts are similar to the metal and beam-hardening artefacts seen in traditional attenuation-based X-ray computed tomography (CT) even though they tend to be more severe and have a different physical basis. A particularly worrisome part of this type of artifact is the fact that it spreads broadly across a wide area on CT image even when the dense tissue responsible for it localized.

>Read more on the Photon Factory website

Image: A rat foot model of rheumatoid arthritis. Left: Absorption image, Middle: Phase image using conventional algorithms, and Right: phase image employing the proposed algorithm. All images were taken at the BL-14C, Photon Factory, KEK.