science
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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 10005 -
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 10736 -
Structure of Neuron-Connecting Synaptic Adhesion Molecules Discovered
A research team has found the three-dimensional structure of synaptic adhesion molecules, which orchestrate synaptogenesis. The research findings also propose the mechanism of synapses in its initial formation. Some brain diseases such as obsessive compulsive disorder (OCD) or bipolar disorders arise from a malfunction of synapses. The team expects the findings to be applied in investigating pathogenesis and developing medicines for such diseases.
The research was conducted by a Master’s candidate Kee Hun Kim, Professor Ji Won Um from Yonsei University, and Professor Beom Seok Park from Eulji University under the guidance of Professor Homin Kim from the Graduate School of Medical Science and Engineering, KAIST, and Professor Jaewon Ko from Yonsei University. Sponsored by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, the research findings were published online in the November 14th issue of Nature Communications.
A protein that exists in the neuronal transmembrane, Slitrk, interacts with the presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) and forms a protein complex. It is involved in the development of synapses in the initial stage, and balances excitatory and inhibitory signals of neurons.
It is known that a disorder in those two proteins cause a malfunction of synapses, resulting in neuropsychosis such as autism, epilepsy, OCD, and bipolar disorders. However, because the structure as well as synaptogenic function of these proteins were not understood, the development of cures could not progress.
The research team discovered the three-dimensional structure of two synaptic adhesion molecules like Slitrk and LAR-RPTPs and identified the regions of interaction through protein crystallography and transmission electron microscopy (TEM). Furthermore, they found that the formation of the synapse is induced after the combination of two synaptic adhesion molecules develops a cluster.
Professor Kim said, “The research findings will serve as a basis of understanding the pathogenesis of brain diseases which arises from a malfunction of synaptic adhesion molecules. In particular, this is a good example in which collaboration between structural biology and neurobiology has led to a fruitful result.” Professor Ko commented that “this will give new directions to synaptic formation-related-researches by revealing the molecular mechanism of synaptic adhesion molecules.”
Figure 1: Overview of the PTPd Ig1–3/Slitrk1 LRR1 complex.
Figure 2: Representative negative-stained electron microscopy images of Slitrk1 Full ectodomain (yellow arrows indicate the horseshoe-shaped LRR domains). The typical horseshoe-shaped structures and the randomness of the relative positions of each LRR domain can be observed from the two-dimensional class averages displayed in the orange box.
Figure 3: Model of the two-step presynaptic differentiation process mediated by the biding of Slitrks to LAR-RPTPs and subsequent lateral assembly of trans-synaptic LAR-RPTPs/Slitrik complexes.
2014.11.28 View 10964 -
An Artist and Scientist, the Dean of Northwestern University speaks at KAIST
How does an abstract artist look at the world of science? Can art enhance scientific inquiry?
The Department of Chemical and Biomolecular Engineering (CBE), KAIST, invited Professor Julio Mario Ottino to speak at its fourth Annual KAIST CBE Global Distinguished Lectureship from the 15th to 16th October. Professor Ottino is the Dean of the Robert R. McCormick School of Engineering and Applied Science at Northwestern University.
Professor Ottino is a famous artist as well as a scientist. He pursues his disciplines in engineering and art as ways by which an artistic value and scientific truth can coexist. By merging these disciplines, he is praised for adopting balanced engineering education that emphasizes analytical skills and creativity at Northwestern University.
The lecture took place over two days. The topic of the first day was “Creativity” and the next day, “Formalism in Science.”
On the first day, Professor Ottino spoke about “Creativity in Science, Art, and Technology -- How art is separated from science.” He argues that as creativity is essential in art, science, and technology, artistic creativity can help develop scientific and technological creativity.
The next lecture featured “Mixing of Fluids and Solids: Parallels, Divergences, and Lessons.”
He emphasized that the birth of mixing of fluids and researches on granular matter and segregation offered valuable insights and lessons. Although these two topics have developed in different ways, he laid down some examples on how scientific theories have progressed under formalism.
2014.10.16 View 7797 -
Discovery of New Therapeutic Targets for Alzheimer's Disease
A Korean research team headed by Professor Dae-Soo Kim of Biological Sciences at KAIST and Dr. Chang-Jun Lee from the Korea Institute of Science and Technology (KIST) successfully identified that reactive astrocytes, commonly observed in brains affected by Alzheimer’s disease, produce abnormal amounts of inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) in reaction to the enzyme Monoamine oxidase B (Mao-B) and release GABA through the Bestrophin-1 channel to suppress the normal signal transmission of brain nerve cells.
By suppressing the GABA production or release from reactive astrocytes, the research team was able to restore the model mice's memory and learning impairment caused by Alzheimer’s disease. This discovery will allow the development of new drugs to treat Alzheimer’s and other related diseases.
The research result was published in the June 29, 2014 edition of Nature Medicine (Title: GABA from Reactive Astrocytes Impairs Memory in Mouse Models of Alzheimer’s Disease).
For details, please read the article below:
Technology News, July 10, 2014
"Discovery of New Drug Targets for Memory Impairment in Alzheimer’s Disease"
http://technews.tmcnet.com/news/2014/07/10/7917811.htm
2014.07.16 View 8381 -
An Exploratory Study on Smartphone Abuse among College Students
Professor Uichin Lee
Professor Uichin Lee of the Department of Knowledge Service Engineering, KAIST, and his research team developed a system that automatically diagnoses the levels of smartphone addiction based on an analysis of smartphone use records.
Professor Lee investigated the usage patterns of 95 smartphone users (college students) by conducting surveys and interviews and collecting logged data. The research team divided participants into “risk” and “non-risk” groups based on a self-reported rating scale to evaluate their abuse of smartphones. As a result, 36 students were categorized as “high risk” and 59 were categorized as “low risk.”
The researchers collected over 50,000 hours of smartphone use encompassing power levels, screen, battery status, application use, internet use, calling, and texting.
The results showed that the “high risk” group used only 1~2 applications, focusing on mobile messengers (Kakotalk, etc.) and SNS (Facebook, etc.).
In addition, a relationship was found between alarm function and addiction levels. Users who set alarms for Kakaotalk messages and SNS comments used smartphones for an additional 38 minutes per day on average.
Results also showed that “high risk” students were on their smartphones for 4 hours and 13 minutes per day, 46 minutes longer than “low risk” students who used smartphones for 3 hours and 27 minutes. The difference was prevalent during 6 am and noon, and 6pm and midnight. In addition, “high risk” students accessed their smartphones 11.4 times more than “low risk” students.
Based on the collected data, Professor Lee developed an automatic system that distinguished users into “high risk” or “low risk” categories with 80% accuracy. The new system is expected to give an early diagnosis of addiction to smartphone users, thereby allowing for early treatment and intervention before the user becomes addicted.
Professor Lee commented that, "the conventional addiction analysis based on self-analysis surveys did not provide real-time data and were largely inaccurate. The new system overcomes these limitations through data science and personal big data analysis" and that he is "developing an application that monitors smartphone abuse."
Figure 1. Usage amount: overall and application-specific results
Figure 2. Usage frequency: overall and application-specific results
Figure 3. Overall diurnal usage time and frequency
2014.06.05 View 7141 -
An Electron Cloud Distribution Observed by the Scanning Seebeck Microscope
All matters are made of small particles, namely atoms. An atom is composed of a heavy nucleus and cloud-like, extremely light electrons.
Korean researchers developed an electron microscopy technique that enables the accurate observation of an electron cloud distribution at room-temperature. The achievement is comparable to the invention of the quantum tunneling microscopy technique developed 33 years ago.
Professor Yong-Hyun Kim of the Graduate School of Nanoscience and Technology at KAIST and Dr. Ho-Gi Yeo of the Korea Research Institute of Standards and Science (KRISS) developed the Scanning Seebeck Microscope (SSM). The SSM renders clear images of atoms, as well as an electron cloud distribution. This was achieved by creating a voltage difference via a temperature gradient.
The development was introduced in the online edition of Physical Review Letters (April 2014), a prestigious journal published by the American Institute of Physics.
The SSM is expected to be economically competitive as it gives high resolution images at an atomic scale even for graphene and semiconductors, both at room temperature. In addition, if the SSM is applied to thermoelectric material research, it will contribute to the development of high-efficiency thermoelectric materials.
Through numerous hypotheses and experiments, scientists now believe that there exists an electron cloud surrounding a nucleus. IBM's Scanning Tunneling Microscope (STM) was the first to observe the electron cloud and has remained as the only technique to this day. The developers of IBM microscope, Dr. Gerd Binnig and Dr. Heinrich Rohrer, were awarded the 1986 Nobel Prize in Physics.
There still remains a downside to the STM technique, however: it required high precision and extreme low temperature and vibration. The application of voltage also affects the electron cloud, resulting in a distorted image.
The KAIST research team adopted a different approach by using the Seebeck effect which refers to the voltage generation due to a temperature gradient between two materials.
The team placed an observation sample (graphene) at room temperature (37~57℃) and detected its voltage generation. This technique made it possible to observe an electron cloud at room temperature.
Furthermore, the research team investigated the theoretical quantum mechanics behind the electron cloud using the observation gained through the Seebeck effect and also obtained by simulation capability to analyze the experimental results.
The research was a joint research project between KAIST Professor Yong-Hyun Kim and KRISS researcher Dr. Ho-Gi Yeo. Eui-Seop Lee, a Ph.D. candidate of KAIST, and KRISS researcher Dr. Sang-Hui Cho also participated. The Ministry of Science, ICT, and Future Planning, the Global Frontier Initiative, and the Disruptive Convergent Technology Development Initiative funded the project in Korea.
Picture 1: Schematic Diagram of the Scanning Seebeck Microscope (SSM)
Picture 2: Electron cloud distribution observed by SSM at room temperature
Picture 3: Professor Yong-Hyun Kim
2014.04.04 View 12976 -
Is it possible to identify rumors on SNS?
Rumors
sporadically spread with people with fewer followers in the centerResearched
over 100 rumors in the US from 2006 to 2009 Is it
possible to filter information on SNS such as Twitter and Facebook? A research
team led by Professor Mee-Young Cha from the Department of Cultural Technology
Graduate School at KAIST, Professor Kyo-Min Jung of Seoul National University,
Doctor Wei Chen and Yajun Wang of Microsoft Asia, has developed a technology
that can accurately filter out information on Twitter to 90% accuracy. The
research not only deduced a new mathematical model, network structure, and
linguistic characteristics on rumors from SNS data, but is also expected to
enhance the effort to make secure technology to regulate Internet rumors. The team
analysed the characteristics of rumors in over 100 widespread cases in the US
from 2006 to 2009 on Twitter. The team gathered data, which included a range of
areas such as politics, IT, health and celebrity gossips, and their analysis
could identify rumors to 90% accuracy. The filtering was more accurate in
rumors that included slanders or insults. The
research team identified three characteristics of the spread of rumors. Firstly,
rumors spread continuously. Normal news spreads widely once and is mentioned
rarely again on media, but rumors tend to continue for years. Secondly,
rumors spread through sporadic participation of random users with no
connections. Rumors start from people with fewer followers and spread to the
more popular. This phenomenon is often observed in rumors concerning
celebrities or politicians. Lastly,
rumors have unique linguistic characteristics. Rumors frequently include words
(such as “it may be true,” “although not certain, I think,” “although I cannot
fully remember”) related to psychological processes that question, deny, or
infer the reliability of the information. Professor
Cha said, “This research deduced not only a statistical and mathematical model
but also is an integrated research on social psychological theory on the
characteristics of rumors that attract great attention from the society based
on ample data.” The results
were made public in IEEE International Conference on Data Mining last December
in Texas, USA.
2014.02.03 View 9491 -
Two Dimensions of Value: Dopamine Neurons Represent Reward but not Aversiveness
Professor Christopher D. Fiorillo of the Bio & Brain Engineering (http://ineuron.kaist.ac.kr/web/home.html) at KAIST published a research paper in the August 2 issue of Science. The title of the paper is “Two Dimensions of Value: Dopamine Neurons Represent Reward but not Aversiveness.” The following is an introduction of his research work:
To make decisions, we need to estimate the value of sensory stimuli and motor actions, their “goodness” and “badness.” We can imagine that good and bad are two ends of a single continuum, or dimension, of value. This would be analogous to the single dimension of light intensity, which ranges from dark on one end to bright light on the other, with many shades of gray in between. Past models of behavior and learning have been based on a single continuum of value, and it has been proposed that a particular group of neurons (brain cells) that use dopamine as a neurotransmitter (chemical messenger) represent the single dimension of value, signaling both good and bad.
The experiments reported here show that dopamine neurons are sensitive to the value of reward but not punishment (like the aversiveness of a bitter taste). This demonstrates that reward and aversiveness are represented as two discrete dimensions (or categories) in the brain. “Reward” refers to the category of good things (food, water, sex, money, etc.), and “punishment” to the category of bad things (stimuli associated with harm to the body and that cause pain or other unpleasant sensations or emotions).
Rather than having one neurotransmitter (dopamine) to represent a single dimension of value, the present results imply the existence of four neurotransmitters to represent two dimensions of value. Dopamine signals evidence for reward (“gains”) and some other neurotransmitter presumably signals evidence against reward (“losses”). Likewise, there should be a neurotransmitter for evidence of danger and another for evidence of safety. It is interesting that there are three other neurotransmitters that are analogous to dopamine in many respects (serotonin, norepinephrine, and acetylcholine), and it is possible that they could represent the other three value signals.
For the research article, please visit: http://www.sciencemag.org/content/341/6145/546.abstract
For the Science 2nd issue, please visit: http://www.sciencemag.org/content/current#ResearchArticles
Illustration of Value Dimension
2013.08.08 View 7496 -
Prof. Song Chong received the IEEE William R. Bennett Prize Paper Award
The IEEE (Institute of Electrical and Electronics Engineers) Communications Society (ComSoc), a renowned global network of professionals with a common interest in advancing communications technologies, has announced the winner of the 2013 William R. Bennett Prize in the field of communications networking. The prize was given to a Korean research team led by Song Chong, Professor of Electrical Engineering at KAIST and Injong Rhee, Professor of Computer Science at North Carolina State University. In addition, Dr. Minsu Shin, Dr. Seongik Hong, and Dr. Seong Joon Kim of Samsung Electronics Co., Ltd. as well as Professor Kyunghan Lee from Ulsan National Institute of Science and Technology were recognized for their contribution.
The William R. Bennett Prize for communications networking has been awarded each year since 1994 in recognition of the best paper published in any journal financially sponsored or co-sponsored by ComSoc in the previous three calendar years. Only one paper per year is selected based on its quality, originality, scientific citation index, and peer reviews. Among the previous award winners are Robert Gallager of MIT, and Steven Low of the California Institute of Technology, and Kang G. Shin of the University of Michigan.
The Korean research team’s paper, On the Levy-Walk Nature of Human Mobility, was published in the June 2011 issue of IEEE/ACM Transactions on Networking, a bimonthly journal co-sponsored by the IEEE ComSoc, the IEEE Computer Society, and the Association for Computing Machinery (ACM) with its Special Interest Group on Data Communications (SIGCOMM).
In the paper, the research team proposed a new statistical model to effectively analyze the pattern of individual human mobility in daily life. The team handed out GPS (global positioning system) devices to 100 participants residing in five different university campuses in Korea and the US and collected data on their movements for 226 days. The mobility pattern obtained from the experiment predicted accurately how the participants actually moved around during their routines. Since publication, the paper has been cited by other papers approximately 350 times.
The team’s research results will apply to many fields such as the prevention and control of epidemics, the design of efficient communications networks, and the development of urban and transportation system.
The research team received the award on June 10th at the 2013 IEEE International Conference on Communications (ICC) held in Budapest, Hungary, from June 9-13, 2013.
Professor Song Chong
2013.07.06 View 12143 -
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 9412
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Op-Ed by Prof. David Helfman: Global Science and Education in the 21st Century
Professor David Helfman from the Department of Biological Sciences and Graduate School of Nanoscience and Technology(https://sites.google.com/site/cellsignalinglaboratory/home) recently wrote an Op-Ed in the January 2013 issue of Journal of Happy Scientists and Engineers that ispublished by the Ministry of Science, Education and Technology, the Republic of Korea. In the article entitled “Global Science and Education in the 21st Century,” Professor Helfman addressed three important issues in science and education, which will have a great impact for the development of world-leading universities in Korea. For the article, please see the attachment.
2013.01.22 View 10912