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‘Legos of life’ stack together to build proteins

After smashing and dissecting nearly 10,000 proteins to understand their component parts, scientists have discovered the “Legos of life”—four core chemical structures that can be stacked together to build the myriad proteins inside every organism.

The four building blocks make energy available for humans and all other living organisms, according to a new study describing the discovery, which appears in the Proceedings of the National Academy of Sciences.

The findings could lead to applications of these stackable, organic building blocks for biomedical engineering and therapeutic proteins and the development of safer, more efficient industrial and energy catalysts—proteins and enzymes that, like tireless robots, can repeatedly carry out chemical reactions and transfer energy to perform tasks.

“We don’t have a fossil record of what proteins looked like 4 billion years ago, so we have to take what we have today and start walking backwards…”

“Understanding these parts and how they are connected to each other within the existing proteins could help us understand how to design new catalysts that could potentially split water, fix nitrogen, or do other things that are really important for society,” says study coauthor Paul G. Falkowski, a professor who leads the Environmental Biophysics and Molecular Ecology Laboratory at Rutgers University–New Brunswick.

The research was carried out on computers, using data on the 3D atomic structures of 9,500 proteins in the RCSB Protein Data Bank, based at Rutgers, a source of information about how proteins work and evolve.

“We don’t have a fossil record of what proteins looked like 4 billion years ago, so we have to take what we have today and start walking backwards, trying to imagine what these proteins looked like,” says Vikas Nanda, senior author of the study and an associate professor of biochemistry and molecular biology at Rutgers’ Robert Wood Johnson Medical School.

“The study is the first time we’ve been able to take something with thousands of amino acids and break it down into reasonable chunks that could have had primordial origins,” says Nanda.

Certain proteins stay ‘relaxed’ while floating inside cells

The identification of four fundamental building blocks for all proteins is just a beginning. Nanda says future research may discover five or 10 more building blocks that serve as biological Legos.

“Now we need to understand how to put these parts together to make more interesting functional molecules. That’s the next grand challenge,” he explains.

Hagai Raanana, a postdoctoral associate in the Environmental Biophysics and Molecular Ecology Program is the study’s lead author. Doctoral student Douglas H. Pike and postdoctoral associate Eli K. Moore are also coauthors.

Source: Rutgers University

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