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Binding Regulatory Mechanism of Protein Biomolecules Revealed
Professor Hak-Sung Kim
A research team led by Professor Hak-Sung Kim of Biological Sciences, KAIST, and Dr. Mun-Hyeong Seo, KAIST, has revealed a regulatory mechanism that controls the binding affinity of protein’s biomolecules, which is crucial for the protein to recognize molecules and carry out functions within the body.
The research results were published in the April 24th online edition of Nature Communications.
The protein, represented by enzyme, antibody, or hormones, specifically recognizes a variety of biomolecules in all organisms and implements signaling or immune response to precisely adjust and maintain important biological processes. The protein binding affinity of biomolecules plays a crucial role in determining the duration of the bond between two molecules, and hence to determine and control the in-vivo function of proteins.
The researchers have noted that, during the process of proteins’ recognizing biomolecules, the protein binding affinity of biomolecules is closely linked not only to the size of non-covalent interaction between two molecules, but also to the unique kinetic properties of proteins.
To identify the basic mechanism that determines the protein binding affinity of biomolecules, Professor Kim and his research team have made mutation in the allosteric site of protein to create a variety of mutant proteins with the same chemical binding surface, but with the binding affinity vastly differing from 10 to 100 times. The allosteric site of the protein refers to a region which does not directly bind with biomolecules, but crucially influences the biomolecule recognition site.
Using real-time analysis at the single-molecule level of unique kinetic properties of the produced mutant proteins, the researchers were able to identify that the protein binding affinity of biomolecules is directly associated with the protein’s specific kinetic characteristics, its structure opening rate.
Also, by proving that unique characteristics of the protein can be changed at the allosteric site, instead of protein’s direct binding site with biomolecules, the researchers have demonstrated a new methodology of regulating the in-vivo function of proteins.
The researchers expect that these results will contribute greatly to a deeper understanding of protein’s nature that governs various life phenomena and help evaluate the proof of interpreting protein binding affinity of biomolecules from the perspective of protein kinetics.
Professor Kim said, “Until now, the protein binding affinity of biomolecules was determined by a direct interaction between two molecules. Our research has identified an important fact that the structure opening rate of proteins also plays a crucial role in determining their binding affinity.”
[Picture]
A correlation graph of opening rate (kopening) and binding affinity (kd) between protein’s stable, open state and its unstable, partially closed state.
2014.05.02 View 9985 -
Extreme Tech: Nanowire "impossible to replicate" fingerprints could eliminate fraud, counterfeit goods
Research done by Professor Hyun-Joon Song of Chemistry at KAIST on
anti-counterfeit, nanoscale fingerprints generated by randomly distributed
nanowires was introduced by Extreme Tech, an online global science and technology
news.
For the articles, please go to:
Extreme Tech, March 25, 2014Nanowire ‘impossible to replicate’ fingerprints could eliminate fraud, counterfeit goods
http://www.extremetech.com/extreme/179131-nanowire-impossible-to-replicate-fingerprints-could-eliminate-fraud-counterfeit-goods
2014.03.26 View 8604 -
KAIST Holds Open Lecture For Daejeon Residents
Free of cost for any Korean citizen, the registration for the new course opens on the official website from 5th March KAIST’s Department of Humanities and Social Science is currently operating free humanities and liberal arts classes for Daejeon residents.
The theme of the course for this semester is “World and Politics,” which will begin on 13th March and run every Thursday for 6 weeks at KAIST’s International Seminar Room.
This course has been organized to introduce the general public to the current political situation with neighboring countries such as China, Japan and North Korea, as well as the characteristics of multinational companies.
Top experts in the related fields will give lectures. First, Professor Ha-Yong Jung from Kyunghee University will talk on “American liberalism and democracy”; Professor Gyeong-Mo An from Korea National Defense University on “Kim Jeong-Eun and the Future of North Korea--Is the Collapse of North Korea A Reality?” and Ja-Seon Koo, a visiting professor at Korea National Diplomatic Academy on “The Chinese Communist Party during the Xi Jinping Period.”
“With the era of globalization, the political situations in the neighboring countries have both direct and indirect effects on our lives,” said Professor Hyeon-Seok Park who has organized the courses. "These classes will be an opportunity for our citizens to understand and learn about the current affairs in the world.”
Anyone can attend the course, and registration is from March 5th to 9th at the official webpage of KAIST’s Humanities and Social Sciences Department (http://hss.kaist.ac.kr). All the courses are free of charge.
Contact: Department of Humanities and Social Science Research (Tel. 350-4687, E-mail: baobab@kaist.ac.kr)
2014.03.06 View 6872 -
Professor Suk-Bok Chang receives 14th Korea Science Award in the field of Chemistry
Professor Suk-Bok Chang from the Department of Chemistry at KAIST received the “2013 Korea Science Award” in chemistry hosted by the National Research Foundation and the Ministry of Science, ICT, and Future Planning, Republic of Korea.
The Korea Science Award is a presidential award of Korea, which was first established in 1987 to recognize research excellence in natural science. Three scientists are selected for the award in every other year.
Professor Chang primarily researches the catalyzing mechanism of carbon-hydrogen bonds in organic molecules. He has succeeded in making great progress in the field of organic chemistry especially in developing a new type of transition metal catalytic behavior that can be applied to low-reactivity compounds.
Hydrocarbons are abundant in nature, but its unreactive nature in ambient conditions makes it unsuitable as reactant for compound synthesis. In addition, the mechanism behind transition metal catalyzed carbon-hydrogen bond synthesis has not been proven sufficiently.
The prediction that fossil fuels will be depleted before the end of the century makes hydrocarbon synthesis an extremely important matter.
The need for an effective hydrocarbon synthesis method inspired Professor Chang to pursue research in the transition metal catalysis method and to develop a catalytic system that would allow efficient synthesis even in ambient conditions.
Professor Chang has been the lead researcher for the Institute for Basic Science’s “molecule catalysis reaction research team” since December 2012 and has been carrying out this research in KAIST.
2014.01.27 View 10743 -
Mechanism in regulation of cancer-related key enzyme, ATM, for DNA damage and repair revealed
Professor Kwang-Wook Choi
A research team led by Professor Kwang-Wook Choi and Dr. Seong-Tae Hong from the Department of Biological Sciences at KAIST has successfully investigated the operational mechanism of the protein Ataxia Telangiectasia Mutated (ATM), an essential protein to the function of a crucial key enzyme that repairs the damaged DNA which stores biometric information. The results were published on December 19th Nature Communications online edition.
All organisms, including humans, constantly strive to protect the information within their DNA from damages posed by a number of factors, such as carbonized materials in our daily food intake, radioactive materials such as radon emitting from the cement of buildings or ultraviolet of the sunlight, which could be a trigger for cancer.
In order to keep the DNA information safe, the organisms are always carrying out complex and sophisticated DNA repair work, which involves the crucial DNA damage repair protein ATM. Consequently, a faulty ATM leads to higher risks of cancer.
Until now, academia predicted that the Translationally Controlled Tumor Protein (TCTP) will play an important role in regulating the function of ATM. However, since most of main research regarding TCTP has only been conducted in cultured cells, it was unable to identify exactly what mechanisms TCTP employs to control ATM.
The KAIST research team identified that TCTP can combine with ATM or increase the enzymatic activity of ATM. In addition, Drosophilia, one of the most widely used model organisms for molecular genetics, has been used to identify that TCTP and ATM play a very important role in repairing the DNA damaged by radiation. This information has allowed the researchers to establish TCTP’s essential function in maintaining the DNA information in cell cultures and even in higher organisms, and to provide specific and important clues to the regulation of ATM by TCTP.
Professor Kwang-Wook Choi said, “Our research is a good example that basic research using Drosophilia can make important contributions to understanding the process of diseases, such as cancer, and to developing adequate treatment.”
The research has been funded by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea.
Figure 1. When the amount of TCTP protein is reduced, cells of the Drosophila's eye are abnormally deformed by radiation. Scale bars = 200mm
Figure 2. When the amount of TCTP protein is reduced, the chromosomes of Drosophilia are easily broken by radiation. Scale bars = 10 mm.
Figure 3. When gene expressions of TCTP and ATM are reduced, large defects occur in the normal development of the eye. (Left: normal Drosophilia's eye, right: development-deficient eye)
Figure 4. ATM marks the position of the broken DNA, with TCTP helping to facilitate this reaction. DNA (blue line) within the cell nucleus is coiled around the histone protein (green cylinder). When DNA is broken, ATM protein attaches a phosphate group (P). Multiple DNA repair protein recognizes the phosphate as a signal that requires repair and gathers at the site.
2014.01.07 View 13275 -
Professor Yong-Hee Lee of Physics Received the Humboldt Research Award
In recognition of his past accomplishments in research and teaching, Professor Yong-Hee Lee of Physics at KAIST received the Humboldt Research Award in November 2013. The Humboldt Research Award is annually given by the Alexander von Humboldt Foundation to internationally renowned scientists and scholars in the fields of biology, chemistry, computer science, economics, linguistics, management, mathematics, medicine, philosophy, and physics. The winners of the award are offered with 60,000 Euros of research grant as well as an opportunity to undertake prolonged periods of research in collaboration with researchers in Germany.Professor Lee, who may be the first Korean physicist receiving the award, plans to conduct joint research with colleagues at the Technical University of Berlin and University of Würzburg.
2014.01.05 View 8747 -
KAIST Student Awarded Prize from Energy Saving Contest
Jun-Min Kwon, an undergraduate student in the Department of Chemistry at KAIST, was awarded a prize from the Ministry of Trade, Industry and Energy, Republic of Korea, at the 35th Energy Saving Contest which was held on November 20.
The student club he has been leading was also selected as one of the best groups by the Save Energy Save Earth (SESE), a volunteer organization supported by the Korea Energy Management Corporation and the Ministry of Knowledge Economy, Republic of Korea.
Kwon began promoting energy conservation through a blog and participated in related meetings and workshops as a high school student to improve the understanding on the importance of energy saving and recycling.He also received awards from the Second National Assembly Forum on Climate Change, the Korean National Science Fair, as well as the Samsung Human Tech Paper Award.
2013.12.24 View 12486 -
Nanoparticle based Super Lens selected as 2013 Science and Technology News
Professor Yong-keun Park
"Nanoparticle-based Super Lens", an article by KAIST Physics Department’s Professor Yong-keun Park and Professor Yong-hoon Cho’s joint research team, has been selected as one of the ten representative 2013 Science and Technology News, by the Korea Federation of Science and Technology Societies.
This new concept super lens uses the scattering of light, which can yield over three times more superior resolution of previous optical lenses.
Unlike the conventional optical lens that utilizes refraction of the light, the super lens can give the image of viruses and structure within the cell at 100㎚. This lens is also applicable to state-of-the-art optical and semiconductor processes.
In addition, this year's research achievements also include the successful launch of Naro, a new technology to remove the brain cell membrane which gives a more transparent view of the brain, a new drug to inhibit cancer metastasis, as well as the development of ultra-wide-angle insect eye camera technology.
Articles for 2013 Science and Technology News are chosen in three trial reviews by committee and online voting by 5,437 people over the course of [two weeks]14 days, from November 21st to December 4th.
2013.12.14 View 10519 -
Therapy developed to induce Angiogenesis of Retina
- Junyeop Lee, Graduate School of Medical Sciences and Engineering
- Research results expected to be applied for treatment of diabetic retinopathy
A major clue to treatment of retinovascular disease, which causes blindness, has been found. The key to protection of the retinal nerve is the angiogenic protein that promotes healthy retinal vessel growth around the retina, which usually does not receive blood supply readily. This research offers a beginning to the possible improvement of therapy for diabetic retinopathy1 and retinopathy of prematurity2. Also important to the research is the fact that the ophthalmology specialist researcher, currently undergoing professional training, provided the results.
KAIST Graduate School of Medical Sciences and Engineering’s Junyeop Lee is the opthalmology specialist, who carried out the research under supervision by academic advisers Gyuyeong Go and Wookjun Yoo. The Ministry of Science, ICT and Future Planning as well as the National Research Foundation of Korea have funded his research. The research results have been published as a cover paper on ‘Science Translational Medicine’ on 18th August. This journal is a sister publication of Science, which is prestigious in the field of translational medicine that ties the basic science with clinical medicine. (Thesis title: Angiopoietin-1 Guides Directional Angiogenesis Through Integrin αvβ5 Signaling for Recovery of Ischemic Retinopathy)
The traditional treatment of diabetic retinopathy includes laser photocoagulation to destroy the retinal tissues or antibody therapeutics, which prevents vessel proliferation and blood leaking. The advantage of antibody therapeutics3 is that it retains the retinal nerves, however, it is not the fundamental solution but merely a temporary one, which requires repeated treatments.
The research team identified that Angiopoietin-14 protein, known as essential for growth and stabilization of vessels, also plays an important role in retinal vessel growth. The protein protects the retinal nerves, as well as provides improvement for retinal ischemia5 that is the root cause of vision loss due to retinal hemorrhages. It is expected to become a key to finding fundamental treatment method – by providing sufficient blood supply to the retina, thereby preserving the retinal nerve functions.
The results show that administration of Angiopoietin-1 to retinopathy mouse model promotes growth of healthy vessel growth, further preventing abnormal vessel growth, retinal hemorrhage and vision loss due to retinal ischemia.
Junyeop Lee said, “This research has identified that Angiopoietin-1 is an important factor in retinal vessel generation and stabilization. The paradigm will shift from traditional treatment method, which prevents vessel growth, to a new method that generates healthy vessels and strengthens vessel functions.”
1 Diabetic retinopathy: This retinovascular disease is a diabetic complication caused by insufficient blood supply. It is the major causes of blindness in adults.
2 Retinopathy of prematurity: The retinal vascular disease that occurs in premature infants with incomplete retinal vascular development. It is also the most common cause of blindness in children.
3 Antibody Therapeutics: Antibody developed to selectively inhibit abnormal blood vessel growth and leakage. Typical antibody therapeutics is Avastin and Lucentis, which hinder vascular endothelial growth factor (VEGF).
4 Angiopoietin-1: A critical growth factor that induces the production of healthy blood vessels and maintains the stability of the created vessel.
5 Retinal ischemia: State of ailment where retinal tissue blood supply is not sufficient.
Figure 1. Retinopathy mouse models show that, in comparison to the control group, the VEGF-Trap treatment and Angiopoietin-1 (Ang1) treatment groups significantly suppresses the pathological vascular proliferation. In addition, the Ang 1 group show vessel growth toward the central avascular area (region of retinal ischemia), which is not observed in VEGF-Trap treatment.
Figure 2. Reduced retinal ischemia, retinal bleeding and blood vessel normalization by Angiopoietin-1. Retinal ischemic region (arrow) and retinal bleeding significantly reduced in the Angiopoietin-1 (Ang1) treatment model in comparison to control group (left). The newly generated vessels in Ang 1 model are structurally supported by perivascular cells as normal retinal vessels do (right).
2013.10.12 View 11564 -
New Structural Insight into Neurodegenerative Disease
A research team from the Korea Advanced Institute of Science and Technology (KAIST) released their results on the structure and molecular details of the neurodegenerative disease-associated protein Ataxin-1. Mutations in Ataxin-1 cause the neurological disease, Spinocerebella Ataxia Type 1 (SCA1), which is characterized by a loss of muscular coordination and balance (ataxia), as is seen in Parkinson’s, Alzheimer’s, and Huntington’s diseases.
SCA1-causing mutations in the ATAXIN1 gene alter the length of a glutamine stretch in the Ataxin-1 protein. The research team provides the first structural insight into the complex formation of ATAXIN-1 with its binding partner, Capicua (CIC). The team, led by Professor Ji-Joon Song from the Department of Biological Sciences at KAIST, solved the structure of Ataxin-1 and CIC complex in atomic level revealing molecular details of the interaction between Ataxin-1 and CIC.
Professor Song explained his recent research work,
“We are able to see the intricate process of complex formation and reconfiguration of the two proteins when they interact with each other. Our work, we expect, will provide a new therapeutic target to modulate SCA1 neurodegenerative disease.”
Understanding structural and molecular details of proteins at the atomic level will help researchers to track the molecular pathogenesis of the disease and, ultimately, design targeted therapies or treatments for patients, rather than just relieving the symptoms of diseases.
Professor Song’s research paper, entitled “Structural Basis of Protein Complex Formation and Reconfiguration by Polyglutamine Disease Protein ATAXIN-1 and Capicua,” will be published in the March 15th issue of Genes & Development (www.genesdev.org).
Complex Formation and Reconfiguration of ATAXIN-1 and Capicua
The complex formation between a polyglutamine disease protein, ATXIN-1 and the transcriptional repressor Capicua (CIC) plays a critical role in SCA 1 pathogenesis. The image shows that the homodimerization of ATXIN-1 (yellow and red) is disrupted upon binding of CIC (blue). Furthermore, the binding of CIC to the ATXIN-1 induces a new form of ATXIN-1 dimerization mediated by CICs (ATXIN-1 AXH domains are shown in yellow and red, and CIC peptides shown in blue and white).
2013.04.02 View 9305 -
Ligand Recognition Mechanism of Protein Identified
Professor Hak-Sung Kim
-“Solved the 50 year old mystery of how protein recognises and binds to ligands”
- Exciting potential for understanding life phenomena and the further development of highly effective therapeutic agent development
KAIST’s Biological Science Department’s Professor Hak-Sung Kim, working in collaboration with Professor Sung-Chul Hong of Department of Physics, Seoul National University, has identified the mechanism of how the protein recognizes and binds to ligands within the human body.
The research findings were published in the online edition of Nature Chemical Biology (March 18), which is the most prestigious journal in the field of life science.
Since the research identified the mechanism, of which protein recognises and binds to ligands, it will take an essential role in understanding complex life phenomenon by understanding regulatory function of protein.
Also, ligand recognition of proteins is closely related to the cause of various diseases. Therefore the research team hopes to contribute to the development of highly effective treatments.
Ligands, well-known examples include nucleic acid and proteins, form the structure of an organism or are essential constituents with special functions such as information signalling.
In particular, the most important role of protein is recognising and binding to a particular ligand and hence regulating and maintaining life phenomena. The abnormal occurrence of an error in recognition of ligands may lead to various diseases.
The research team focused on the repetition of change in protein structure from the most stable “open form” to a relatively unstable “partially closed form”.
Professor Kim’s team analysed the change in protein structure when binding to a ligand on a molecular level in real time to explain the ligand recognition mechanism.
The research findings showed that ligands prefer the most stable protein structure. The team was the first in the world to identify that ligands alter protein structure to the most stable, the lowest energy level, when it binds to the protein.
In addition, the team found that ligands bind to unstable partially-closed forms to change protein structure.
The existing models to explain ligand recognition mechanism of protein are “Induced Custom Model”, which involves change in protein structure in binding to ligands, and the “Structure Selection Model”, which argues that ligands select and recognise only the best protein structure out of many. The academic world considers that the team’s research findings have perfectly proved the models through experiments for the first time in the world.
Professor Kim explained, “In the presence of ligands, there exists a phenomenon where the speed of altering protein structure is changed. This phenomenon is analysed on a molecular level to prove ligand recognition mechanism of protein for the first time”. He also said, “The 50-year old mystery, that existed only as a hypothesis on biology textbooks and was thought never to be solved, has been confirmed through experiments for the first time.”
Figure 1: Proteins, with open and partially open form, recognising and binding to ligands.
Figure 2: Ligands temporarily bind to a stable protein structure, open form, which changes into the most stable structure, closed form. In addition, binding to partially closed form also changes protein structure to closed form.
2013.04.01 View 11599 -
Op-Ed by Professor David Helfman: Global Science and Education in Korea for the 21st Century
Professor David Helfman from the Department of Biological Sciences and Graduate School of Nanoscience and Technology contributed an op-ed, “Global Science and Education in Korea for the 21st Century, to the Korea Herald on February 20, 2013. For the article, please click the link below:
http://www.koreaherald.com/view.php?ud=20130220000623.
2013.02.26 View 10527