Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Classifies, Analyzes Protein-Protein Interfaces

16.12.2010
Interactions between proteins are at the heart of cellular processes, and those interactions depend on the interfaces where the direct physical contact occurs.

A new study published this week suggests that there may be roughly a thousand structurally-distinct protein-protein interfaces – and that their structures depend largely on the simple physics of the proteins.

Believed to be the first systematic study of the nature of the protein-protein interfaces, the research could help explain the phenomena of “promiscuous” proteins that bind to many other proteins. The results could also have implications for the development of drug compounds designed to affect these protein-protein interactions.

“Proteins and the rules of protein-protein interactions are the result of very simple physical principles,” said Jeffrey Skolnick, director of the Center for the Study of Systems Biology at the Georgia Institute of Technology. “In this study, we set out to characterize the nature of the interfaces – the structures of the interfaces – in all known protein structures. We wanted to ask how much of the interface could be explained purely by the structural features of the proteins without involving evolution or intelligent design.”

A paper describing the research was published Dec. 13 in the early edition of the journal Proceedings of the National Academy of Sciences. The work was sponsored by the National Institutes of Health (NIH).

Skolnick and collaborator Mu Gao studied the structural similarity of protein-protein interfaces involving interactions between dimers, developing an efficient computational method called iAlign to classify the interfaces known to exist among native proteins. They found that even without structural similarity between the individual monomers that form dimeric complexes, roughly 90 percent of the interfaces had a close structural neighbor.

“We found that in the library of protein-protein structures that nature has available, there are about a thousand structurally-distinct interfaces,” said Skolnick, who is a Georgia Research Alliance Eminent Scholar in computational systems biology. “You can have very different types of protein structures adopting the same interface, but it was still surprising to see such a small number.”

To obtain the kind of bonding measured experimentally requires that interfaces have sufficient surface area, so Skolnick believes most interfaces are roughly planar, much like two Nerf balls pressed together. “If you take this spherical interface and blunt it, that creates a much larger surface interface, so most of the interfaces that we saw are actually planar,” he said. “You need to have enough sticky surface area.”

To separate the role of the proteins’ basic physical structure from the effects of the amino acids that they gain through an evolutionary process, the researchers studied a set of synthetic homopolypeptide proteins created totally in the computer to mimic natural proteins. After conducting docking tests on these “toy proteins” decorated with random amino acids, Skolnick and Gao observed 90 percent of the interfaces that they had previously characterized in the natural proteins.

“This suggests that the interfaces we see are features of the protein structure and the protein physics,” Skolnick said. “Proteins seem to be primed by their physical characteristics to enable these higher-order molecular interactions to occur with a significant probability. The capacity is a feature of the structure.”

That means the interfaces are independent of the kind of secondary structure that each protein has and uncoupled from the global fold that each protein adopts. “If the interaction between the proteins doesn’t depend on the internal geometry of the structure or the secondary type of folding, that allows the possibility of having one protein interface with many interactions,” Skolnick said.

The planar nature of the interfaces and their similarity could help explain the promiscuity observed among a number of proteins. If the surfaces were highly specific, it wouldn’t be possible for these proteins to interact with so many different proteins.

“If you have a background capacity to interact, then you could imagine that this is the origin of a lot of promiscuous interactions that you see in cells,” he said. “The surfaces are essentially complementary, and by accident you happen to have an appropriate constellation of amino acids. The more stable interactions clearly need to have undergone some kind of selection procedure to stabilize them enough to stick.”

Skolnick believes that the basic physics of the proteins therefore forms a foundation on which evolution – everything the protein encounters – can act. “We are examining the basic rules of the road that evolution takes advantage of over time,” he said.

Understanding these rules helps clarify the complex operation of cellular structures – and potentially give drug designers a new pathway to exploit.

“Promiscuity of interactions appears to be a feature of biological systems, and this bears on drug discovery,” Skolnick said. “There are now very few drugs that inhibit protein-protein interactions because of the surface areas that are involved. Knowing the nature of these interfaces and the rules governing them might allow us to figure out how to design an inhibitor better.”

Knowledge that protein interfaces are primed for promiscuity helps explains the observations in biology, but open up some new questions. For one, how do cells maintain order if each protein can interact with many other proteins?

“It may be like being at a crowded New Year’s Eve party in which everybody is wearing weak flypaper,” Skolnick suggested. “How do you reach the person you want to meet when you are sticking to people you don’t want to interact with? How do you assemble anything useful when all the parts stick together?”

Abby Vogel Robinson | Newswise Science News
Further information:
http://www.gatech.edu

More articles from Studies and Analyses:

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>