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Mystery in Membrane Traffic How NSF Disassembles Single SNAR Complex Solved
KAIST researchers discovered that the protein N-ethylmaleimide-sensitive factor (NSF) unravels a single SNARE complex using one round ATP turnover by tearing the complex with a single burst, contradicting a previous theory that it unwinds in a processive manner. In 2013, James E. Rothman, Randy W. Schekman, and Thomas C. Südhof won the Nobel Prize in Physiology or Medicine for their discoveries of molecular machineries for vesicle trafficking, a major transport system in cells for maintaining cellular processes. Vesicle traffic acts as a kind of “home-delivery service” in cells. Vesicles package and deliver materials such as proteins and hormones from one cell organelle to another. Then it releases its contents by fusing with the target organelle’s membrane. One example of vesicle traffic is in neuronal communications, where neurotransmitters are released from a neuron. Some of the key proteins for vesicle traffic discovered by the Nobel Prize winners were N-ethylmaleimide-sensitive factor (NSF), alpha-soluble NSF attachment protein (α-SNAP), and soluble SNAP receptors (SNAREs). SNARE proteins are known as the minimal machinery for membrane fusion. To induce membrane fusion, the proteins combine to form a SNARE complex in a four helical bundle, and NSF and α-SNAP disassemble the SNARE complex for reuse. In particular, NSF can bind an energy source molecule, adenosine triphosphate (ATP), and the ATP-bound NSF develops internal tension via cleavage of ATP. This process is used to exert great force on SNARE complexes, eventually pulling them apart. However, although about 30 years have passed since the Nobel Prize winners’ discovery, how NSF/α-SNAP disassembled the SNARE complex remained a mystery to scientists due to a lack in methodology. In a recent issue of Science, published on March 27, 2015, a research team, led by Tae-Young Yoon of the Department of Physics at the Korea Advanced Institute of Science and Technology (KAIST) and Reinhard Jahn of the Department of Neurobiology of the Max-Planck-Institute for Biophysical Chemistry, reports that NSF/α-SNAP disassemble a single SNARE complex using various single-molecule biophysical methods that allow them to monitor and manipulate individual protein complexes. “We have learned that NSF releases energy in a burst within 20 milliseconds to “tear” the SNARE complex apart in a one-step global unfolding reaction, which is immediately followed by the release of SNARE proteins,” said Yoon. Previously, it was believed that NSF disassembled a SNARE complex by unwinding it in a processive manner. Also, largely unexplained was how many cycles of ATP hydrolysis were required and how these cycles were connected to the disassembly of the SNARE complex. Yoon added, “From our research, we found that NSF requires hydrolysis of ATPs that were already bound before it attached to the SNAREs—which means that only one round of an ATP turnover is sufficient for SNARE complex disassembly. Moreover, this is possible because NSF pulls a SNARE complex apart by building up the energy from individual ATPs and releasing it at once, yielding a “spring-loaded” mechanism.” NSF is a member of the ATPases associated with various cellular activities family (AAA+ ATPase), which is essential for many cellular functions such as DNA replication and protein degradation, membrane fusion, microtubule severing, peroxisome biogenesis, signal transduction, and the regulation of gene expression. This research has added valuable new insights and hints for studying AAA+ ATPase proteins, which are crucial for various living beings. The title of the research paper is “Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover.” (DOI: 10.1126/science.aaa5267) Youtube Link: https://www.youtube.com/watch?v=FqTSYHtyHWE&feature=youtu.be Picture 1. Working model of how NSF/α-SNAP disassemble a single SNARE complex Picture 2. After neurotransmitter release, NSF disassembles a single SNARE complex using a single round of ATP turnover in a single burst reaction.
Professor Sangyong Jon Appointed Fellow of AIMBE
Professor Sangyong Jon of the Department of Biological Sciences at KAIST has been appointed a member of the American Institute for Medical and Biological Engineering (AIMBE) fellowship. Established in 1991, AIMBE is a non-profit organization based in Washington, D.C., representing 50,000 individuals and the top 2% of medical and biological engineers. AIMBE provides policy advice and advocacy for medical and biological engineering for the benefit of humanity. It has had about 1,500 fellows over the past 25 years. Among the members, only 110 are non-American nationalities. Following the appointment of Dr. Hae-Bang Lee, the former senior researcher at the Korean Research Institute of Chemical Technology, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, Professor Jon is the third Korean to become an AIMBE fellow. He had an induction ceremony for the appointment of his fellowship at the AIMBE’s Annual Event held on March 15-17, 2015 in Washington, D.C. An authority on nanomedicine, Professor Jon has developed many original technologies including multi-functional Theranostics nano particles for the diagnosis and treatment of diseases. He received the Most Cited Paper Award from Theranostics, an academic journal specialized in nanomedicine, last February. Additionally, Professor Jon is a leading researcher in the field of translational medicine, using a multi-disciplinary, highly collaborative, “Bench to Bedside” approach for disease treatment and prevention. He created a biotechnology venture company and transferred research developments to the industry in Korea.
The Real Time Observation of the Birth of a Molecule
From right to left: Dr. Kyung-Hwan Kim, Professor Hyotcherl Lhee, and Jong-Gu Kim, a Ph.D. candidate Professor Hyotcherl Lhee of the Department of Chemistry at KAIST and Japanese research teams jointly published their research results showing that they have succeeded in the direct observation of how atoms form a molecule in the online issue of Nature on February 19, 2015. The researchers used water in which gold atoms ([Au(CN) 2- ]) are dissolved and fired X-ray pulses over the specimen in femtosecond timescales to study chemical reactions taking place among the gold atoms. They were able to examine in real time the instant process of how gold atoms bond together to become a molecule, to a trimer or tetramer state. This direct viewing of the formation of a gold trimer complex ([Au(CN) 2- ] 3 ) will provide an opportunity to understand complex chemical and biological systems. For details, please see the following press release that was distributed by the High Energy Accelerator Research Organization, KEK, in Japan: Direct Observation of Bond Formations February 18, 2015 A collaboration between researchers from KEK, the Institute for Basic Science (IBS), the Korea Advanced Institute of Science and Technology (KAIST), RIKEN, and the Japan Synchrotron Radiation Research Institute (JASRI) used the SACLA X-ray free electron laser (XFEL) facility for a real time visualization of the birth of a molecular that occurs via photoinduced formation of a chemical bonds. This achievement was published in the online version of the scientific journal “Nature” (published on 19 February 2015). Direct “observation” of the bond making, through a chemical reaction, has been longstanding dream for chemists. However, the distance between atoms is very small, at about 100 picometer, and the bonding is completed very quickly, taking less than one picosecond (ps). Hence, previously, one could only imagine the bond formation between atoms while looking at the chemical reaction progressing in the test-tube. In this study, the research group focused on the process of photoinduced bond formation between gold (Au) ions dissolved in water. In the ground state (S 0 state in Fig. 1) Au ions that are weakly bound to each other by an electron affinity and aligned in a bent geometry. Upon a photoexcitation, the S 0 state rapidly converts into an excited (S 1 state in Fig. 1) state where Au-Au covalent bonds are formed among Au ions aligned in a linear geometry. Subsequently, the S 1 state transforms to a triplet state (T 1 state in Fig. 1) in 1.6 ps while accompanying further contraction of Au-Au bonds by 0.1 Å. Later, the T 1 state of the trimer converts to a tetramer (tetramer state in Fig. 1) on nanosecond time scale. Finally, the Au ions returned to their original loosely interacting bent structure. In this research, the direct observation of a very fast chemical reaction, induced by the photo-excitation, was succeeded (Fig. 2, 3). Therefore, this method is expected to be a fundamental technology for understanding the light energy conversion reaction. The research group is actively working to apply this method to the development of viable renewable energy resources, such as a photocatalysts for artificial photosynthesis using sunlight. This research was supported by the X-ray Free Electron Laser Priority Strategy Program of the MEXT, PRESTO of the JST, and the the Innovative Areas "Artificial Photosynthesis (AnApple)" grant from the Japan Society for the Promotion of Science (JSPS). Publication: Nature , 518 (19 February 2015) Title: Direct observation of bond formation in solution with femtosecond X-ray scattering Authors: K. H. Kim 1 , J. G. Kim 1 , S. Nozawa 1 , T. Sato 1 , K. Y. Oang, T. W. Kim, H. Ki, J. Jo, S. Park, C. Song, T. Sato, K. Ogawa, T. Togashi, K. Tono, M. Yabashi, T. Ishikawa, J. Kim, R. Ryoo, J. Kim, H. Ihee, S. Adachi. ※ 1: These authors contributed equally to the work. DOI: 10.1038/nature14163 Figure 1. Structure of a gold cyano trimer complex (Au(CN) 2 - ) 3 . Figure 2. Observed changes in the molecular structure of the gold complex Figure 3. Schematic view of the research of photo-chemical reactions by the molecular movie
Press Release on Piezoelectric Nanogenerators of ZnO with Aluminium Nitride Stacked Layers by the American Institute of Physics
The American Institute of Physics (AIP) released a news article entitled “Zinc Oxide Materials Tapped for Tiny Energy Harvesting Devices” on January 13, 2015. The article described the research led by Professor Giwan Yoon of the Electrical Engineering Department at KAIST. It was published in the January 12, 2015 issue of Applied Physics Letters. AIP publishes the journal. For the news release, please visit the link below: The American Institute of Physics, January 13, 2015 “Zinc Oxide Materials Tapped for Tiny Energy Harvesting Devices” New research helps pave the way toward highly energy-efficient zinc oxide-based micro energy harvesting devices with applications in portable communications, healthcare and environmental monitoring, and more http://www.aip.org/publishing/journal-highlights/zinc-oxide-materials-tapped-tiny-energy-harvesting-devices
KAIST Announces the Recipients of Distinguished Alumni Awards
The KAIST Alumni Association (KAA) announced four “Proud KAIST Alumni” awards recipients for the year 2014: Sung-Wook Park, the Chief Executive Officer and President of SK Hynix; Seung Ho Shin, the President of Kangwon National University; Kew-Ho Lee, the President of the Korea Research Institute of Chemical Technology; and Mun-Kee Choi, the former Minister of Science, ICT and Future Planning of the Republic of Korea. The award ceremony took place during the 2015 KAA’s New Year's ceremony on January 17, 2015 at the Palace Hotel in Seoul. Sung-Wook Park (M.S. ’82 and Ph.D. ’88, Department of Materials Science and Engineering), the Chief Executive Officer and President of SK Hynix, has worked as an expert in the field of memory semi-conductors for the past 30 years. He developed innovative technology and improved production efficiency, enabling the Korean semi-conductor industry to become a global leader. Seung Ho Shin (M.S. ’79 and Ph.D. ’87, Department of Physics), the President of Kangwon National University (KNU), worked in the field of optical information processing, producing excellent research achievements and teaching the next generation of scientists. As the president of KNU, he has set an exemplary leadership in higher education. Kew-Ho Lee (M.S. ’75, Department of Chemistry), the President of the Korea Research Institute of Chemical Technology, pioneered the field of separation film production which contributed greatly to Korean technological developments. He led several domestic and international societies to facilitate dynamic exchanges between industry and academia and with the international community. Mun-Kee Choi (M.S. ’76, Department of Industrial and Systems Engineering), the former Minister of Science, ICT and Future Planning, the Republic of Korea, is a great contributor to the information and communications technology in Korea, working as a leader in the field of broadband integrated service digital network. He is also an educator for gifted students in science and technology, and a manager of the Electronics and Telecommunications Research Institute. The Alumni Association established the “Proud KAIST Alumni Awards” in 1992 to recognize its alumni’s outstanding contributions to Korea and KAIST. Pictured from left to right, Sung-Wook Park (the Chief Executive Officer and President of SK Hynix), Seung Ho Shin (the President of Kangwon National University), Kew-Ho Lee (the President of the Korea Research Institute of Chemical Technology), and Mun-Kee Choi (the former Minister of Science, ICT and Future Planning)
A Key Signal Transduction Pathway Switch in Cardiomyocyte Identified
A KAIST research team has identified the fundamental principle in deciding the fate of cardiomyocyte or heart muscle cells. They have determined that it depends on the degree of stimulus in β-adrenergic receptor signal transduction pathway in the cardiomyocyte to control cells' survival or death. The findings, the team hopes, can be used to treat various heart diseases including heart failure. The research was led by KAIST Department of Bio and Brain Engineering Chair Professor Kwang-Hyun Cho and conducted by Dr. Sung-Young Shin (lead author) and Ph.D. candidates Ho-Sung Lee and Joon-Hyuk Kang. The research was conducted jointly with GIST (Gwangju Institute of Science and Technology) Department of Biological Sciences Professor Do-Han Kim’s team. The research was supported by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea. The paper was published in Nature Communications on December 17, 2014 with the title, “The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes.” The β-adrenergic receptor signal transduction pathway can promote cell survival (mediated by β2 receptors), but also can result in cell death by inducing toxin (mediated by β1 receptors) that leads to various heart diseases including heart failure. Past attempts to identify the fundamental principle in the fate determining process of cardiomyocyte based on β-adrenergic receptor signalling concluded without much success. The β-adrenergic receptor is a type of protein on the cell membrane of cardiomyocyte (heart muscle cell) that when stimulated by neurohormones such as epinephrine or norepinephrine would transduce signals making the cardiomyocyte contract faster and stronger. The research team used large-scale computer simulation analysis and systems biology to identify ERK* and ICER** signal transduction pathways mediated by a feed-forward circuit as a key molecular switch that decides between cell survival and death. Weak β-adrenergic receptor stimulations activate ERK signal transduction pathway, increasing Bcl-2*** protein expression to promote cardiomyocyte survival. On the other hand, strong β-adrenergic receptor stimulations activate ICER signal transduction pathway, reducing Bcl-2 protein expression to promote cardiomyocyte death. Researchers used a systems biology approach to identify the mechanism of B-blocker****, a common drug prescribed for heart failure. When cardiomyocyte is treated with β1 inhibitor, strong stimulation on β-adrenergic receptor increases Bcl-2 expression, improving the chance of cardiomyocyte survival, a cell protection effect. Professor Kwang-Hyun Cho said, “This research used systems biology, an integrated, convergence research of IT (information technology) and BT (biotechnology), to successfully identify the mechanism in deciding the fate of cardiomyocytes based on the β-adrenergic receptor signal transduction pathway for the first time. I am hopeful that this research will enable the control of cardiomyocyte survival and death to treat various heart diseases including heart failure.” Professor Cho’s team was the first to pioneer a new field of systems biology, especially concerning the complex signal transduction network involved in diseases. Their research is focused on modelling, analyzing simulations, and experimentally proving signal pathways. Professor Cho has published 140 articles in international journals including Cell, Science, and Nature. * ERK (Extracellular signal-regulated kinases): Signal transduction molecule involved in cell survival ** ICER (Inducible cAMP early repressor): Signal transduction molecule involved in cell death *** Bcl-2 (B-cell lymphoma 2): Key signal transduction molecule involved in promotion of cell survival **** β-blocker: Drug that acts as β-adrenergic receptor inhibitor known to slow the progression of heart failure, hence used most commonly in medicine. Picture: A schematic diagram for the β-AR signalling network
Elsevier Selects a KAIST Graduate's Paper as the Top Cited Papers in 2011-2012
Dr. Myung-Won Seo, a graduate from the Department of Chemical and Bimolecular Engineering at KAIST, published a paper in January 2011 in Chemical Engineering Journal, which was entitled “Solid Circulation and Loop-seal Characteristics of a Dual Circulating Fluidized Bed: Experiments and CFD Simulation.” His paper was selected by Elsevier as the Top Cited Papers of 2011-2012. The Chemical Engineering Journal is a renowned peer-reviewed journal issued by Elsevier. Dr. Seo published another paper, “CFD Simulation with Experiments in a Dual Circulating Fluidized Bed Gasifier,” in January 2012 in Computers & Chemical Engineering, which was also selected as the Most Downloaded Papers in 2012-2013. Dr. Seo graduated with a doctoral degree from KAIST in 2011. He is currently working at the Clean Fuel Laboratory, the Korea Institute of Energy Research, Daejeon, as a researcher. His research areas are coal gasification, upgrading, and liquefaction, as well as energy and chemical production from low-grade fuels such as biomass and wastes.
3D Printer Developed by KAIST Undergraduate Students
More than 100 Pre-orders Prior to Product Launch Made KAIST undergraduate students received more than 100 pre-orders before the launch for 3D printers they developed and became a hot topic of interest. KAIST Research Institute for Social Technology and Innovations (Head Hong-Kyu Lee) had a launch party at Daejeon Riviera Hotel on 17 November 2014 for “Commercial Delta 3D Printer” developed by KAIST undergraduate students inviting around 50 businesses, buyers and representatives of 3D Printing Industry Association. “3D Printer” uses blueprints of products such as toys, mug cups and chairs to make 3D objects and is thought to be revolutionary technology in manufacturing industry. The interest has grown as recent printers could print even fruits and cosmetics. The printing structure of 3D printer can be divided roughly into horizontal Mendel method and Delta method. KAIST students focused on the Delta method to give a differentiated product from 90% of commercial products that use Mendel method. First, the students focused on lowering the cost of unit price by using self-developed components. The carriage (transport machine) of the product is replaced by self-developed components instead of bearing to reduce the noise and the linking method was changed to beads from loop guide to increase the completeness of the printed product. Also, an auto-levelling is loaded to ensure the nozzle and the bed is parallel and hence increasing convenience for the users. Further, the printer, designed by a product designer in Germany, is linked to a smartphone application for blueprints. A student in the development team, Seokhyeon Seo (Department of Computer Science, 3rd Year Undergraduate) said, “The biggest merits of the product are lowering the price to a 1/3 by using self-developed components and reducing the noise.” He continued, “By using a smartphone application, anyone can easily design the product. So it is applicable to use for education or at home” In the exhibit, “3D Printing Korea 2014,” in Coex, Seoul the printer had a preview demonstration, and received more than 100 pre-orders from educational and business training institutions. Further, buyers from Canada and the US requested opening agencies in their countries. KAIST Research Institute for Social Technology and Innovations Head Hong-Kyu Lee said, “3D printing is an innovative technology that could bring the 3rd industrial revolution.” He continued, “It is still early days but the demand will increase exponentially.” This project was a research project of KAIST Research Institute for Social Technology and Innovations led by a development team consisting of 4 undergraduate students of KAIST, one student from University of Oxford and one German product designer. Students in the picture below are Won-Hoi Kim (Department of Mechanical Engineering), Sung-Hyun Cho (Department of Mechanical Engineering), and Suk-Hyun Seo (Department of Computer Science) from left to right.
Professor Joong-Keun Park Receives SeAH Heam Academic Award
Professor Joong-Keun Park of the Department of Materials Science and Engineering at KAIST received an award from SeAH Steel Corp. in recognition of his academic achievements in the field of metallic and materials engineering. The award was presented at the 2014 Fall Conference of the Korean Institute of Metals and Materials which took place on October 22-24 at the Kangwon Land Convention Hotel. The award, called “SeAH Heam Academic Award,” is given annually to a scholar who has contributed to the development of new metal and polymer composite materials and its related field in Korea. Following the award ceremony, Professor Park gave a keynote speech on ferrous metals for automotive materials.
KAIST and Samsung Heavy Industries Celebrate 20 Years of Cooperation
KAIST and Samsung Heavy Industries (SHI) celebrated the twentieth anniversary of their university-industry cooperation in shipbuilding and ocean technology research. Established in 1995, the cooperation has remained steadfast for two decades, even times when Korea suffered gravely from its financial crisis in late 1990s. A ceremony to commemorate the cooperation took place at the Mechanical Engineering Building on October 17, 2014. About thirty distinguished guests including the Head of the Department of Mechanical Engineering, Professor Choong-Sik Bae, and the chief engineer of SHI Marine Research Institute, Dr. Jong-Soo Seo, participated in the ceremony. The cooperation programs included appointing advisory professors for technological support, implementing business-based academic courses, offering university-industry wide open lectures, opening regular courses for auditing, and finding possible joint researches. Through this cooperation, Samsung has secured technologies needed for industry, and KAIST has produced students who have real-world experience in industrial fields. Twenty years of cooperation has produced shining results by running various programs such as technological advice, special lectures, small-scale research projects, consignment research projects, and courses for research and design personnel. For example, what started as a small-scale research project with USD 4,800 in funding, the LNG (Liquefied Natural Gas) related research has grown into a large-scale research project with a total of USD 2.85 million in funding. As a result, they developed a secondary barrier for LNG carriers which was recognized by Lloyd‘s Register. Their research eventually lowered ship manufacturing costs tremendously. In 2003, the cooperation project received the presidential citation from the University-Industry Cooperation Competition organized by the Federation of Korean Industries. KAIST and SHI planned to increase their cooperation to make it Korea’s leading university-industry cooperation program. Professor Bae said, “Our programs to focus on solving industrial problems have turned out quite successful.” He emphasized that “for this reason, the cooperation even continued during the Asian financial crisis in 1997.” He added, “By expanding the current cooperation, we aim to make it an exemplary program that contributes to Korea’s shipbuilding and ocean plant industries.”
KAIST Registers an Internationally Recognized Standard Patent
A video compression technology, jointly developed by Professor Mun-Chul Kim of the Department of Electrical Engineering at KAIST, the Electronics and Telecommunications Research Institute (ETRI), and the Korean Broadcasting System (KBS), is registered internationally as the standard patent in the next-generation High Efficiency Video Coding (HEVC). HEVC (H.265) is an international technology standard that compresses large image data for Ultra High Definition (UHD) televisions and smartphones. It has the twice the compression efficiency as that of H.264/AVC which is most commonly used for processing full HD sources. This means that it is able to compress a video file to half the size while maintaining the same image quality. Although the related market is at a nascent stage, HEVC technology has already been applied to the latest version of televisions and smartphones. Experts predict that the market will grow to USD 200 billion by 2016, and KAIST is expected to receive a royalty payment of USD 9.3 million from this patent. The International Organization for Standardization (ISO/IEC) established the HEVC standard in January 2013. Also, an international patent pool licensing corporation, MPEG LA announced the HEVC standard patent pool on September 29, 2014. Professor Joongmyeon Bae, Dean of the Office of University-Industry Cooperation (OUIC) of KAIST, said, “This is an unprecedented case for Korea whereby a core technology developed by a university became an international standard, which has a vast impact on the market.” President of KAIST, Steve Kang commented, “With its advanced technology, KAIST joined the HEVC standard patent pool as one of the 23 founding members along with Apple, Siemens, and NEC. This is a remarkable achievement.” Picture 1: Improvements in video compression technology Picture 2: Comparison of different screen resolutions
KAIST Co-owns the HEVC Patent Portfolio License
MPEG LA, LLC, a firm based in Denver, Colorado, which licenses patent pools covering essential patents required for the use of video coding technology, such as MPEG-2, MPEG-4 Visual (Part 2), and HEVC/H.264, announced the availability of the High Efficiency Video Coding (HEVC) Patent Portfolio License on September 29, 2014. The HEVC standard, also known as H.265 and MPEG-H Part 2, is necessary to improve video coding and transmission efficiency for the Internet, televisions, and mobile gadgets with increased speed and capacity. Through the portfolio license, users can easily obtain patent rights required for the HEVC standard in a single transaction, instead of negotiating separate licenses from multiple patent holders. A total of 23 enterprises currently own essential HEVC patents. KAIST is the only Korean university among the joint patent owners. Collaborating with the Korea Broadcasting System (KBS) and the Electronics and Telecommunications Research Institute (ETRI), Professor Mun-Chul Kim of the Electrical Engineering Department at KAIST developed one of the core patents. For a link to a press release distributed by MPEG LA, LLC, please see: MPEG LA, LLC, September 29, 2014 "MPEG LA, LLC Offers HEVC Patent Portfolio License" http://www.mpegla.com/main/Pages/Media.aspx
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