Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deciphering the mechanism of an ion pump

19.12.2011
Insights obtained from a structural and functional analysis of an ion-pumping protein could benefit future drug discovery efforts

From an analysis of the sodium-transporting vacuolar ATPases (V-ATPases) of the bacterium Enterococcus hirae, Takeshi Murata of the RIKEN Systems and Structural Biology Center, Yokohama, and colleagues recently obtained valuable structural and functional information about a process that pumps protons and other positively charged ions across cellular membranes1.


Figure 1: The crystal structure of the E. hirae V-ATPase with molecules of DCCD (green spheres) bound to E139 at each individual subunit.
Copyright : 2011 Takeshi Murata

Adenosine triphosphate (ATP) is the primary energy ‘currency’ within cells, and numerous enzymes are powered by the metabolic processing of this molecule via a mechanism known as hydrolysis. V-ATPases can exploit this process to pump positively charged ions across cellular membranes. This process occurs at the junction between a rotating ‘K’ domain and a fixed ‘a’ domain within the segment of the protein that resides at the cell membrane, although the specifics remain unclear.

N,N’-dicyclohexylcarbodiimide (DCCD), a chemical that selectively reacts with a specific glutamate amino acid (E139) within the sodium-binding pockets of the K ring, proved valuable in assessing this protein’s function. The researchers demonstrated that DCCD inhibited sodium binding by nearly 30-fold, but that this inhibition was sharply reduced when the enzyme was pretreated with sodium ions, suggesting that the two molecules interact with overlapping targets within the ring.

The K ring is composed of ten identical subunits, and DCCD efficiently reacts with E139 in each of these individual components (Fig. 1). By gathering structural data from the DCCD-treated V-ATPase, Murata and colleagues obtained a snapshot of what the protein looks like in the absence of sodium, which they could in turn compare against the structure of the sodium-bound form.

Although the two structures were largely similar, DCCD treatment triggered a change in E139 that locked the sodium binding sites into an ‘open’ structure that prevented ion retention. The negative charge of E139 made an important contribution to the binding of the positively charged Na+ ion; DCCD appeared to work by neutralizing this charge. The researchers hypothesize that a similar process governs ion release during the transport process; as the K domain rotates, each subunit’s E139 interacts with a positively charged amino acid on the domain, triggering ion release and transfer across the membrane.

Confirming this model will require additional structural data. “We would like to obtain the structure of [the] whole complex containing both the rotor ring and a-subunit,” Murata says. Nevertheless, these findings could prove immediately applicable to the development of more effective ATPase inhibitors, a class of drugs potentially useful for treating cancer and other diseases. “V-ATPases are of considerable pharmacological interest,” says Murata.

The corresponding author for this highlight is based at the Systems and Structural Biology Team, RIKEN Systems and Structural Biology Center

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht The world's tiniest first responders
21.06.2018 | University of Southern California

nachricht A new toxin in Cholera bacteria discovered by scientists in Umeå
21.06.2018 | Schwedischer Forschungsrat - The Swedish Research Council

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Better model of water under extreme conditions could aid understanding of Earth's mantle

21.06.2018 | Earth Sciences

What are the effects of coral reef marine protected areas?

21.06.2018 | Life Sciences

The Janus head of the South Asian monsoon

21.06.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>