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Essential Science: World Wide Web reveals protein secrets

The research reviews a discovery of a previously overlooked site located on protein molecules. This site may solve a conundrum about how proteins are able to carry out specialized functions within living cells.

The discovery related to small fragments of molecular material (which the scientists have called “add-ons”). The material is the outer edge of the protein interface which helps to customize what a protein can actually do. The term “add-ons” was selected since the proteins customize the interface between proteins in a similar way to how software add-ons customize a web interface with the computer user.

Why is protein structure important?

The work is important since proteins enable the chemical reactions that occur in cells (enzymes); bind to foreign invaders in the body and kill them (antibodies); together with thousands of other critical functions. To ensure these functions happen, proteins need to connect with each other and form protein complexes.

To find the answers, the biologists drew upon mathematics and geometry and they were inspired by the way the World Wide Web is constructed. These principles were used to investigate the 20 known amino acids that connect together to form long chains, and which then fold up to form proteins. From the 1,000 known protein geometries in nature, proteins are further able to form complexes that perform hundreds of thousands of critical functions.

The type of interface region has been known about for a while; however, it was unclear where the interfaces actually connect with other proteins. Moreover, scientists have been unsure how key proteins are able to detect each other within a crowded cellular environment. This is a remarkable biological process, since cellular environments will contain tens of thousands of other proteins.

What did the research entail?

The Ohio State University, working with colleagues from the University of Regensburg, has reported how the add-ons function to enable proteins to connect exclusively with the correct partner. This ensures that proteins are able to interact in specific ways. In all the researchers analyzed the protein sequences taken from over 15,000 bacterial and archaeal genomes located on a large computer cluster. These were then sorted using computer programs (big data analytics) to group proteins which shared common evolutionary ancestors. These were grouped into a kind of family tree and compared.

Testing out the theory using bacteria

A Bacillus species bacterium growing on a Petri-dish (from Tim Sandle s laboratory)

A Bacillus species bacterium growing on a Petri-dish (from Tim Sandle’s laboratory)

To test this out, the researchers undertook studies using viable bacteria. These experiments used a modified bacterium called Bacillus subtilis. The organism was developed to have a unique interface add-on missing. With this in place, the bacterial colonies grew 80 percent less, in terms of mass, under laboratory conditions. This happened because the missing interface add-on resulted in atypical cross-interactions of proteins occurring within the B. subtilis cells.

One of the lead researchers, Dr. Maximilian Plach, explains the background to the study in a research briefing. Dr. Plach states: “Much work has been put into analyzing how proteins interact with each other and what the interfaces look like, how they are constructed, and how they evolved.”

The protein research has been published in the journal of the Proceedings of the National Academy of Sciences. The research paper is titled “Evolutionary diversification of protein–protein interactions by interface add-ons.”

Essential Science

Graphene is an allotrope of carbon in the form of a two-dimensional  atomic-scale  honey-comb lattic...

Graphene is an allotrope of carbon in the form of a two-dimensional, atomic-scale, honey-comb lattice in which one atom forms each vertex.
Courtesy: National Science Foundation

This article is part of Digital Journal’s regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Last week’s topic was on next-generation fuel cells and how the ‘wonder material’ graphene plays a pivotal role in developing appropriate electrodes to maximize fuel cell efficiency.

The week before we profiled the work of Austin Russell who is a pioneer in the type of technology that helps cars see. At age 13 Russell pioneered optics and photonics; at 18 he set up the company Luminar, with support from PayPal. Now he is launching an advanced LiDAR system.

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Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, business, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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