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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.
2015.03.28 View 10789 -
KAIST Develops a Credit-Card-Thick Flexible Lithium Ion Battery
Since the battery can be charged wirelessly, useful applications are expected including medical patches and smart cards.
Professor Jang Wook Choi at KAIST’s Graduate School of Energy, Environment, Water, and Sustainability (EEWS) and Dr. Jae Yong Song at the Korea Research Institute of Standards and Science jointly led research to invent a flexible lithium ion battery that is thinner than a credit card and can be charged wirelessly.
Their research findings were published online in Nano Letters on March 6, 2015. Lithium ion batteries are widely used today in various electronics including mobile devices and electronic cars. Researchers said that their work could help accelerate the development of flexible and wearable electronics.
Conventional lithium ion batteries are manufactured based on a layering technology, stacking up anodes, separating films, and cathodes like a sandwich, which makes it difficult to reduce their thickness. In addition, friction arises between layers, making the batteries impossible to bend. The coating films of electrodes easily come off, which contributes to the batteries’ poor performance.
The research team abandoned the existing production technology. Instead, they removed the separating films, layered the cathodes and anodes collinearly on a plane, and created a partition between electrodes to eliminate potential problems, such as short circuits and voltage dips, commonly present in lithium ion batteries.
After more than five thousand consecutive flexing experiments, the research team confirmed the possibility of a more flexible electrode structure while maintaining the battery performance comparable to the level of current lithium ion batteries.
Flexible batteries can be applied to integrated smart cards, cosmetic and medical patches, and skin adhesive sensors that can control a computer with voice commands or gesture as seen in the movie “Iron Man.”
Moreover, the team has successfully developed wireless-charging technology using electromagnetic induction and solar batteries.
They are currently developing a mass production process to combine this planar battery technology and printing, to ultimately create a new paradigm to print semiconductors and batteries using 3D printers.
Professor Choi said, “This new technology will contribute to diversifying patch functions as it is applicable to power various adhesive medical patches.”
Picture 1: Medical patch (left) and flexible secondary battery (right)
Picture 2: Diagram of flexible battery
Picture 3: Smart card embedding flexible battery
2015.03.24 View 12383 -
KVIP Opened in Pangyo
KAIST has opened the KAIST Venture Innovation Program (KVIP) in its Center for Industry Outreach, designed for executive and high-ranking officers of venture companies. Located in Pangyo Techno Valley, KAIST’s Center for Industry Outreach was established in collaboration with the government of Gyeonggi Province to support venture companies in Pangyo for business management training, venture networking, and university-industry cooperation.
The program will be held every Monday for 12 weeks from April 13 to July 6 in KAIST’s Center for Industry Outreach. This executive education program mainly focuses on solving problems that arise when a medium-sized venture company is in the course of growing into a global corporation. The program is divided into four courses which will cover business management, competition in the global market, transformation of a company, and technological innovation.
Professors from various departments at KAIST will give lectures on their fields. Professor Jaeseung Jeong from the Bio and Brain Engineering Department, Professor Hoi-Jun Yoo from the Electrical Engineering Department, Professor Sangmin Bae from the Industrial Design Department, and Professor Kwangjae Sung from the Business and Technology Management Department will each deliver lectures on brain engineering, semiconductor, design, and restructuring.
Industry experts are also invited to give talks, including Dr. Dae-Gyu Byun, the Chief Executive Officer and President of HUMAX Electronics, Dr. Gwang-Cheol Choi, the Chief Executive Officer of SK Engineering & Construction, Mr. Il-young Kim, the former Chief Executive Officer of KT, Dr. Jae-hoon Jeong, the President of the Korea Institute for the Advancement of Technology (KIAT), Dr. Intak Bae, the Chief Executive Officer of Summit Partners, and Mr. Kyung-taek Kwak, a film director.
The department has started recruiting first round applicants for the program, targeting executive and high-ranking officers of middle-sized venture companies. The details of the program can be found on its website, kvip.kaist.ac.kr.
2015.03.23 View 10566 -
Qualcomm Innovation Award Recognizes 20 KAIST Students
The
award provides research fellowships, worth of USD 100,000, to 20 KAIST graduate
students
With an audience of 100 people present,
KAIST held a ceremony for the Qualcomm Innovation Award 2015 at the Information
Technology Convergence building on campus on March 12, 2015.
The Qualcomm Innovation Award, established
in 2010, is a fellowship that supports innovative science and engineering master’s
and doctoral students at KAIST. Qualcomm donated USD 100,000 to KAIST, stipulating that it be used to foster a creative research environment for graduate
students.
To select the recipients, KAIST formed an award committee chaired
by Professor Soo-Young Lee of the Department of Electrical Engineering and accepted research proposals until late January.
The award committee first selected 37
proposals from 75 papers submitted and then chose the final 20 research
proposals on March 12, 2015 after presentation evaluations. The presentations had to show promise of innovation and creativity; prospective influence on wireless communications
and mobile industry; and the prospect of being implemented.
Each recipient received a USD 4,500 research
fellowship along with an opportunity to present their research findings at a
workshop where Qualcomm engineers and other distinguished individuals of the industry
will attend.
Previously, Qualcomm has donated
research fellowships to KAIST graduate students in 2011 and 2013.
2015.03.19 View 10028 -
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.
2015.03.12 View 12574 -
Interactions Features KAIST's Human-Computer Interaction Lab
Interactions, a bi-monthly magazine published by the Association for Computing Machinery (ACM), the largest educational and scientific computing society in the world, featured an article introducing Human-Computer Interaction (HCI) Lab at KAIST in the March/April 2015 issue (http://interactions.acm.org/archive/toc/march-april-2015).
Established in 2002, the HCI Lab (http://hcil.kaist.ac.kr/) is run by Professor Geehyuk Lee of the Computer Science Department at KAIST. The lab conducts various research projects to improve the design and operation of physical user interfaces and develops new interaction techniques for new types of computers. For the article, see the link below:
ACM Interactions, March and April 2015
Day in the Lab: Human-Computer Interaction Lab @ KAIST
http://interactions.acm.org/archive/view/march-april-2015/human-computer-interaction-lab-kaist
2015.03.02 View 10267 -
Professor Sang Yup Lee Appointed Founding Board Member of Cell Systems
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed a member of the founding editorial board of the newly established journal Cell Systems.
Cell Systems will be a sister journal of Cell, one of the three most prestigious scientific journals along with Nature and Science, that publishes a wide range of papers on biological engineering. The first issue of Cell Systems will be published this July.
Cell Systems plans to publish innovative discoveries, reviews of various research instruments, and research findings on integrated and quantified systems in the field of biology.
Professor Lee is a pioneer in metabolic engineering of microorganism with a focus on biopolymers and metabolites production. He is the editor-in-chief of Biotechnology Journal and serves on the editorial board of numerous international journals. He is also a member of the Global Agenda Council of the World Economic Forum and the Presidential Advisory Committee on Science and Technology in Korea.
Professor Lee said, “Cell Systems will present research findings that discuss whole biological systems methodically.” He continued, “I hope many research findings of Korean scholars will be published in Cell Systems, which will become a representative journal of systems biology and systems biological engineering.”
2015.02.13 View 9543 -
Professor Kwang-Hyun Cho Recognzied by "Scientist of the Month" Award
Professor Kwang-Hyun Cho of KAIST’s Department of Bio and Brain Engineering received the “Scientist of the Month” award in February 2015 from the Ministry of Science, ICT, and Future Planning of the Republic of Korea and the National Research Foundation of Korea. The award was in recognition of Professor Cho’s contribution to the advanced technique of controlling the death of cancer cells based on systems biology, a convergence research in information technology (IT) and biotechnology.
Professor Cho has published around 140 articles in international journals, including 34 papers in renowned science journals such as Nature, Science, and Cell in the past three years. His work also includes systems biology textbooks and many entries in international academic encyclopaedia.
His field, systems biology, is a new biological research paradigm that identifies and controls the fundamental principles of organisms on a systems level.
A well-known tumour suppressor protein, p53, is known to suppress abnormal cell growth and promote apoptosis of can cells, and thus was a focus of research by many scientists, but its effect has been insignificant and brought many side effects. This was due to the complex function of p53 that controls various positive and negative feedbacks. Therefore, there was a limit to understanding the protein with the existing biological approach.
However, Professor Cho found the kinetic change and function of p53 via a systems biology approach. By applying IT technology to complex biological networks, he also identified the response to stress and the survival and death signal transduction pathways of cardiomyocytes and developed new control methods for cancer cells.
Professor Cho said, “This award served as a momentum to turn over a new leaf.” He added, “I hope convergence research such as my field will bring more innovative ideas on the boundaries of academia.”
2015.02.09 View 12831 -
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
2015.02.04 View 32812 -
Danish Minister for Higher Education and Science Visits KAIST
Sofie Carsten Nielsen, the Minister for Higher Education and Science of Denmark, accompanied by her delegation, visited KAIST on January 21, 2015 to study outstanding cases of creative economy and to discuss methods of cooperation.
Her delegation included other distinguished members including Thomas Lehmann, the Danish ambassador to Korea, Peter Olesen, Chairman of Innovation Foundation Denmark Governing Board, and Martin Bendsøe, Senior Vice President and Dean of Technical University of Denmark.
After attending the "Electronic Communication Double Degree Agreement" signing ceremony between KAIST’s Department of Electrical Engineering and the Technical University of Denmark, Minister Nielsen visited KAIST’s Institute of Entrepreneurship to observe bilateral industry-university collaborations between KAIST and Denmark and discussed future development plans.
Also, the Grundfos Student Innovation Camp, sponsored by Grundfos, the world's largest pump manufacturer based in Denmark, took place at KAIST from October 26-31, 2014 where Grundfos professionals as well as students from Seoul National University, KAIST, and Technical University of Denmark (DTU) exchanged ideas and opinions on energy efficiency.
KAIST is currently conducting 19 collaborative projects including seven joint researches and seven joint degrees with DTU.
Minister Sofie Carsten Nielsen stands fifth from the left in the front row in the first picture below.
2015.01.27 View 9425 -
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)
2015.01.19 View 14451 -
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
2015.01.05 View 13569