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 Water world
20.11.2017 | Washington University in St. Louis

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>