Showing posts with label structure. Show all posts
Showing posts with label structure. Show all posts

Monday, 5 August 2013

Scientists solve structure of infection tool used by Yersinia bacterium

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Biology / Biochemistry
Article Date: 03 Aug 2013 - 0:00 PDT Current ratings for:
Scientists solve structure of infection tool used by Yersinia bacterium
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Abdominal pain, fever, diarrhoea - these symptoms could point to an infection with the bacterium Yersinia. The bacterium's pathogenic potential is based on a syringe-like injection apparatus called injectisome. For the first time, an international team of researchers including scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, has unraveled this molecular syringe's spatial conformation. The researchers were able to demonstrate that the length of Yersinia's injectisome's basal body, which crosses the bacterial cell wall, is adjustable - very likely an adaptation to physical stress.

The rod-shaped bacterium Yersinia enterocolitica, which is transmitted through contaminated food, causes gastrointestinal diseases. In Germany alone, several thousand cases are reported annually. Yersinia uses a rather sophisticated tool - its injection apparatus - to infect humans. Not only does the apparatus look like a syringe, it actually serves a similar purpose. A molecular "needle", which sticks out from the bacterium's surface, extends across the bacterial membranes to the host cell. It is through this needle that the bacterium "injects" substances that facilitate infection of the host. Now, for the first time, an interdisciplinary team of HZI scientists together with their colleagues at the Biozentrum of the University of Basel and at the Ecole Polytechnique Fédérale de Lausanne in Switzerland, has presented the structure of Yersinia enterocolitica's injectisome in high-resolution and 3D. They published their results in the digital scientific magazine eLife.

Their innovative approach has yielded surprising results. Previous studies had been concerned with isolating the molecular syringe from the bacterium and studying it under the electron microscope. "We, however, actually studied the injectisome in situ, in other words, on the bacterial surface, right where it normally occurs," explains Prof. Henning Stahlberg, University of Basel. To this end, the researchers cooled the bacteria to minus 193 degrees Celsius and used cryo-electron microscopy to take pictures of the syringe from various angles. They then computed a spatial structure from a set of two-dimensional images - a highly effective method for examining large molecular complexes. The syringe, which consists of some 30 different proteins, definitely falls into that category.

When comparing over 2000 single syringes from over 300 bacteria, the researchers made a surprising discovery: "There is a range of different lengths of each injection apparatus' base - in some cases, it's on the order of ten nanometers, or ten millionth of a millimeter. It can be stretched or compressed - just like a spring," explains Dr. Stefan Schmelz of the HZI, one of the study's first authors. As much as we consider such dimensions to be miniscule - to a bacterium, which itself is but a hundred times that size, they are substantial. "Bacteria are exposed to considerable forces, be it during contact with other cells or upon changes in environmental salinity," explains Prof. Dirk Heinz, the HZI's scientific director and former head of the HZI Department of Molecular Structural Biology. "If the injectisomes were rigidly constructed, bacteria would most likely be unable to resist these forces. Their cell walls would simply rupture."

Insights into the structure of Yersinia's attack tool offer clues as to ways in which the molecular syringe may be therapeutically inhibited. Without this apparatus, the bacteria are practically harmless. "Also other pathogenic bacteria make use of this principle during infection, for example Salmonella that cause food poisoning," confirms Dr. Mikhail Kudryashev, another of the study's primary authors and a researcher at the University of Basel. The team was already able to document this same flexibility in Shigella, the causative agent behind bacillary dysentery. The "molecular building kit," as Schmelz calls it, is highly similar, suggesting that insights from this current study can potentially also be applied to other pathogenic bacteria.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject.

Mikhail Kudryashev, Marco Stenta, Stefan Schmelz, Marlise Amstutz, Ulrich Wiesand, Daniel Castaño-Díez, Matteo T Degiacomi, Stefan Münnich, Christopher KE Bleck, Julia Kowal, Andreas Diepold, Dirk W Heinz, Matteo Dal Peraro, Guy R Cornelis, Henning Stahlberg. In situ structural analysis of the Yersinia enterocolitica injectisome, eLife, 2013, DOI: 10.7554/elife.00792

Helmholtz Centre for Infection Research

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Tuesday, 30 July 2013

New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals

Main Category: Biology / Biochemistry
Also Included In: Pharma Industry / Biotech Industry
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals
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Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. Their findings were published online in Nature.

"Our research clarifies the nature of this previously mysterious inactivation state. This gives us better understanding of fundamental biology and should improve the rational design of drugs, which often target the inactivated state of channels" said Benoît Roux, PhD, professor of biochemistry and molecular biology at the University of Chicago.

Potassium channels, present in the cells of virtually living organisms, are core components in bioelectricity generation and cellular communication. Required for functions such as neural firing and muscle contraction, they serve as common targets in pharmaceutical development.

These proteins act as a gated tunnel through the cell membrane, controlling the flow of small ions into and out of cells. After being activated by an external signal, potassium channels open to allow ions through. Soon after, however, they close, entering an inactive state and are unable to respond to stimuli for 10 to up to 20 seconds.

The cause of this long recovery period, which is enormously slow by molecular standards, has remained a mystery, as structural changes in the protein are known to be almost negligible between the active and inactivated states - differing by a distance equivalent to the diameter of a single carbon atom.

To shed light on this phenomenon, Roux and his team used supercomputers to simulate the movement and behavior of every individual atom in the potassium channel and its immediate environment. After computations corresponding to millions of core-hours, the team discovered that just 12 water molecules were responsible for the slow recovery of these channels.

They found that when the potassium channel is open, water molecules quickly bind to tiny cavities within the protein structure, where they block the channel in a state that prevents the passage of ions. The water molecules are released slowly only after the external stimulus has been removed, allowing the channel to be ready for activation again. This computer simulation-based finding was then confirmed through osmolarity experiments in the laboratory.

"Observing this was a complete surprise, but it made a lot of sense in retrospect," Roux said. "Better understanding of this ubiquitous biological system will change how people think about inactivation and recovery of these channels, and has the potential to someday impact human health."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our biology / biochemistry section for the latest news on this subject.

The work was supported by grants from the National Institutes of Health. Computation resources were provided by Oak Ridge National Laboratory, the National Resource for Biomedical Supercomputing and the Pittsburgh Supercomputing Center.

University of Chicago Medical Center

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of Chicago Medical Center. "New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA
University of Chicago Medical Center. (2013, July 30). "New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/264056.php.

Please note: If no author information is provided, the source is cited instead.


'New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals'

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View the original article here

New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals

Main Category: Biology / Biochemistry
Also Included In: Pharma Industry / Biotech Industry
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals
not yet ratednot yet rated

Just 12 molecules of water cause the long post-activation recovery period required by potassium ion channels before they can function again. Using molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom, University of Chicago scientists have revealed this new mechanism in the function of a nearly universal biological structure, with implications ranging from fundamental biology to the design of pharmaceuticals. Their findings were published online in Nature.

"Our research clarifies the nature of this previously mysterious inactivation state. This gives us better understanding of fundamental biology and should improve the rational design of drugs, which often target the inactivated state of channels" said Benoît Roux, PhD, professor of biochemistry and molecular biology at the University of Chicago.

Potassium channels, present in the cells of virtually living organisms, are core components in bioelectricity generation and cellular communication. Required for functions such as neural firing and muscle contraction, they serve as common targets in pharmaceutical development.

These proteins act as a gated tunnel through the cell membrane, controlling the flow of small ions into and out of cells. After being activated by an external signal, potassium channels open to allow ions through. Soon after, however, they close, entering an inactive state and are unable to respond to stimuli for 10 to up to 20 seconds.

The cause of this long recovery period, which is enormously slow by molecular standards, has remained a mystery, as structural changes in the protein are known to be almost negligible between the active and inactivated states - differing by a distance equivalent to the diameter of a single carbon atom.

To shed light on this phenomenon, Roux and his team used supercomputers to simulate the movement and behavior of every individual atom in the potassium channel and its immediate environment. After computations corresponding to millions of core-hours, the team discovered that just 12 water molecules were responsible for the slow recovery of these channels.

They found that when the potassium channel is open, water molecules quickly bind to tiny cavities within the protein structure, where they block the channel in a state that prevents the passage of ions. The water molecules are released slowly only after the external stimulus has been removed, allowing the channel to be ready for activation again. This computer simulation-based finding was then confirmed through osmolarity experiments in the laboratory.

"Observing this was a complete surprise, but it made a lot of sense in retrospect," Roux said. "Better understanding of this ubiquitous biological system will change how people think about inactivation and recovery of these channels, and has the potential to someday impact human health."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our biology / biochemistry section for the latest news on this subject.

The work was supported by grants from the National Institutes of Health. Computation resources were provided by Oak Ridge National Laboratory, the National Resource for Biomedical Supercomputing and the Pittsburgh Supercomputing Center.

University of Chicago Medical Center

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of Chicago Medical Center. "New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA
University of Chicago Medical Center. (2013, July 30). "New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/264056.php.

Please note: If no author information is provided, the source is cited instead.


'New mechanism in the function of a nearly universal biological structure will impact fundamental biology, design of pharmaceuticals'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.



View the original article here