Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find active transporters are universally leaky

03.05.2013
Professor of Biochemistry Emad Tajkhorshid and colleagues have discovered that membrane transporters help not just sugars and other specific substrates cross from one side of a cellular membrane to the other—water also comes along for the ride.

There are two main ways that molecules can cross a membrane. In passive transport, molecules are able to pass through a membrane protein called a channel (which provides a wide open pathway) to get from the high concentration side to low concentration side of the membrane.

This requires no energy as the molecule flows easily down its concentration gradient. In active transport, molecules are pumped by a membrane protein called an active transporter to get from the low concentration side to the high concentration side. This process requires energy, because the molecule must be pumped across the membrane against its natural concentration gradient.

In order to do their job, active transporters use the alternative access mechanism. At first, only one side of the transporter protein is open, allowing only substrate molecules on that side of the membrane to bind to the transporter. Then, a change in the transporter's shape occurs so that first the open side closes, and then the other side of the transporter protein opens, successfully moving the substrate molecule to its destination.

The surprise is that this perfect coordination works only for the main substrate of active transporters, while small molecules such as water seem to be able to sneak through while the protein is undergoing its shape change. The research conducted by the Tajkhorshid group suggests that this is likely a universal behavior for all active membrane transporters and a result of the very large structural changes they undergo.

Researchers study membrane proteins using a tool called molecular dynamics. "All the molecules in biology have to move to do their job. While you can see a lot of nice pictures of proteins showing their structure, but that's just a frozen state," Tajkhorshid said. "In order to describe the function of a biomolecule, you have to see its motion, and molecular dynamics is a nice way to do this. The method essentially solves the Newtonian equations of motion for all the atoms in the molecule we like to study."

The computer simulations involved in molecular dynamics determine the motion of the transporters using algorithms that define how the atoms of a transporter interact with each other, how they interact with solvent, and how they interact with other molecules in the system. These rules are used to calculate the total force acting on every atom at each step of the transporter's motion.

However, challenges arise when doing these computer simulations because of the sheer number of atoms and the small time steps these simulations require.

"Atoms vibrate of a period of 10 femtoseconds [one quadrillionth of a second], so if you want to have ten snapshots nicely showing how it moves, you have to take a picture every one femtosecond to describe the natural motion of the system. Because we have to take such short time steps, calculating even a few microseconds of protein motion becomes computationally very expensive. Thanks to the power provided by the national supercomputing centers we have been able to accomplish such calculations." Tajkhorshid said.

Once these molecular dynamics simulations were up and running, members of Tajkhorshid's lab noticed something that they never expected to see: the transporters were leaking, allowing small amounts of water to pass through along with the substrate.

"Initially, I was surprised, because many people, including myself, assumed that these were perfect machines going back and forth between inward facing and outward facing states," Tajkhorshid said. "For almost two years, my students told me that there was some water passing through, and I just told them to repeat their simulations using more carefully designed setups, and that something was probably wrong with their simulations!"

With a little digging, the researchers found that some other labs had experimentally shown that some transporters did, in fact, have this leaky quality.

"What we did in this work was to propose that it's not just one particular family that has this leakiness, but all of the transporters that we have been studying in the lab. We found that in all cases, every time the protein starts to undergo those large structural changes, leaks form," Tajkhorshid said.

Tajkhorshid likens this mechanism to a scenario familiar to most pet owners.

"When you open the door for someone to come in, the door has to completely open, but that provides access to small things like a dog or a cat to get out of the house. Because transporters move so much when allowing a substrate in, these leaks form, allowing water molecules in," Tajkhorshid said.

Although Tajkhorshid doesn't believe transporter leakiness plays a physiological role in the cell, this discovery adds some interesting new knowledge to the field about transporters.

"Transporters are extremely important proteins, and we would love to understand their function and how they move. If we understand that better, then we might be able to design better, more specific drugs for transporters," Tajkhorshid said.

William Gillespie | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>