Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell membrane proteins give up their secrets

17.07.2014

Rice University researchers apply predictive powers to transmembrane protein folding 

Rice University scientists have succeeded in analyzing transmembrane protein folding in the same way they study the proteins’ free-floating, globular cousins.

Rice theoretical biologist Peter Wolynes and his team at the university’s Center for Theoretical Biological Physics (CTBP) have applied his energy landscape theory to proteins that are hard to view because they live and work primarily inside cell membranes.

The method should increase the technique’s value to researchers who study proteins implicated in diseases and possibly in the creation of drugs to treat them, he said.

The study appeared this week in the Proceedings of the National Academy of Sciences. Lead author Bobby Kim, a graduate student, and co-author Nicholas Schafer, a postdoctoral research associate, are both members of Wolynes’ Rice lab.

Membrane proteins are critical to such functions as photosynthesis and vision, among many others. They can also serve as a cell’s gatekeepers by deciding what may pass through, and also as its gates by helping transport nourishment from the outside and waste from the inside. Because of these multiple roles, they constitute a large percentage of drug targets.

While their function is clear, information about how they fold lags far behind what is available for globular proteins, Wolynes said. “This is strange because membrane proteins are about 30 percent of the genome,” he said.

Wolynes and his colleagues use raw genomic information to predict how strands of amino acids will fold into functional proteins by following paths of least resistance (aka the principle of minimal frustration) dictated by the energy associated with each “bead” in the strand. The closer a protein gets to its functional “native” state, the more stable it becomes. Wolynes’ pioneering theory graphically represents this energy as a funnel.

The researchers test their computer models by comparing them to the structures of actual proteins acquired through X-ray crystallography. Plenty of structures are available for globular folded proteins, which float around the body to carry out tasks essential to life. 

But until recent years, similar structures for transmembrane proteins have been hard to come by because of the difficulty of isolating them for imaging without destroying them. Recent advances use a detergent to wash most of the membrane away from a protein of interest, Wolynes said. “It leaves a fatty layer around the protein but nevertheless gives a sort of coating that allows the whole molecule to form a crystal lattice later on,” he said.

Wolynes was inspired to study membrane proteins when he noticed that two widely used cell biology textbooks were in complete disagreement about how they folded.

“One of them, after listing all the rules, said, ‘This is evidence that it’s kinetically controlled.’ The other said, ‘This is evidence that it’s equilibrium-controlled.’ They’re written in that way of introductory textbooks where anything they tell you about, they act as if it’s absolutely certain. And they were in direct opposition.

“I would say I’m still not certain, but I think our work points much more in the direction that folding is thermodynamically (equilibrium) controlled, at least once the protein is stuck in the membrane.”

Kim and Schafer modified a protein-folding algorithm used by the Wolynes lab called the Associative Memory, Water-Mediated, Structure and Energy Model (AWSEM) to account for outside influences unique to membrane proteins, including the translocon mechanism that inserts partially folded proteins into a membrane, and the membrane itself.

With the algorithm, they successfully determined that thermodynamic funnels still seem to hold the upper hand in folding proteins inside a membrane, as they do for globular proteins.

“We had a database of membrane protein structures from many different labs and we were able to learn the parameters that were transferable between them,” Kim said. “These parameters specify how strongly two residues (the “beads”) should interact and take into account the surrounding environment. That allowed us to make predictions from the raw sequences.”

The researchers expect to fine-tune the AWSEM-membrane algorithm as more structures become available. “I don’t think we’re done learning about membrane interactions,” Wolynes said, suggesting that much of the funneled folding happens after the protein enters the membrane and that very little of it is due to the hydrophobic (kinetic) interactions that play a somewhat larger role in globular protein folding. “My gut feeling is that’s going to be right,” he said.

“The significance of the paper is that we now have an algorithm to predict membrane protein structure pretty well based on the raw genome sequence,” Wolynes said. “This is going to be very useful to interpret a new generation of experiments.”

The National Institutes of Health, through the National Institute of General Medical Sciences, the National Science Foundation (NSF)-supported CTBP and the D.R. Bullard-Welch Chair at Rice University supported the research.

The researchers utilized the Data Analysis and Visualization Cyberinfrastructure (DAVinCI) supercomputer supported by the NSF and administered by Rice’s Ken Kennedy Institute for Information Technology.

Jeff Falk | Eurek Alert!
Further information:
http://news.rice.edu/2014/07/16/cell-membrane-proteins-give-up-their-secrets/

Further reports about: Cell algorithm equilibrium inside interest parameters proteins raw structure structures transmembrane

More articles from Life Sciences:

nachricht Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>