Scientists design protein filaments that snap themselves together like Lego blocks

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Protein filament
This molecular visualization shows how proteins are assembled like building blocks. (UW Illustration)

Researchers have created molecular building blocks that can weave themselves into long threads of protein.

Well, maybe not all that long. Each protein-based building block measures only a nanometer in length, and the self-assembled filaments get about as long as 10,000 nanometers. It’d take more than 2,500 of those filaments, laid end to end, to amount to an inch in total length. Nevertheless, the feat described in this week’s issue of the journal Science demonstrates the power and beauty of protein design.

“Being able to create protein filaments from scratch — or de novo — will help us better understand the structure and mechanics of naturally occurring protein filaments and will also allow us to create entirely novel materials, unlike any found in nature,” senior study author David Baker of the University of Washington said today in a news release.

Baker is a biochemist at the UW School of Medicine and director of UW’s Institute for Protein Design, which has pioneered the protein-folding field for years.

Proteins are complex molecules whose structure typically determines their function. In nature, protein filaments provide the scaffolding for cells and knit together the body’s bones, cartilage, skin and other tissues.

Filament assembly
Computer-designed proteins self-assemble like Lego blocks into filaments that are more than 1,000 times thinner than human hair. (UW Illustration)

Researchers like Baker take advantage of the twists and turns of protein molecules to come up with engineered shapes. There’s even a computer program called Rosetta and a video game called Foldit to help protein designers craft virtual amino acids into a desired shape.

Baker’s team used Rosetta to design small proteins with surface amino acids that latched onto each other in a predetermined way. The small molecules assembled themselves, tier by tier, into a lengthening helix.

“We were eventually able to design proteins that would snap together like Legos,” said Hao Shen, a Ph.D. candidate in molecular engineering. Shen and UW biochemists Jorge Fallas and Eric Lynch are the study’s lead authors.

The researchers found ways to encourage the growth or disassembly of filaments by tinkering with the protein concentration levels in solution, or by adding molecular-scale capping units to inhibit the building process.

Theoretically, proteins could be woven into strands of artificial fibers that equal or surpass the strength of spider silk, which is stronger than steel on a nanometer-by-nanometer basis. But don’t expect to see that application anytime soon, except perhaps in Spider-Man movies. Baker said custom-designed protein filaments are more likely to serve as the scaffolding for new types of diagnostic tests or nano-electronic circuits.

In addition to Hao Shen, Fallas, Lynch and Baker, the authors of “De Novo Design of Self-Assembling Helical Protein Filaments” include William Sheffler, Bradley Parry, Nicholas Jannetty, Justin Decarreau, Michael Wagenbach, Juan Jesus Vicente, Jiajun Chen, Lei Wang, Quinton Dowling, Gustav Oberdorfer, Lance Stewart, Linda Wordeman, James De Yoreo, Christine Jacobs-Wagner and Justin Kollman.

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