Biochemists from the University of Washington have engineered complex protein molecules with additional chemical bonds that make it possible to mix and match them like the base pairs of DNA.
The designer proteins, described today in a paper published by the journal Science, could open the way for a kind of synthetic coding system modeled after the groundbreaking double-helix DNA code system discovered by James Watson and Francis Crick back in 1953.
“Think of it this way: The principle of heredity is Watson-Crick base pairing between the two complementary strands of DNA. We invent in the paper an analogous pairing arrangement for proteins,” David Baker, director of the UW’s Institute for Protein Design, told GeekWire in an email.
Protein molecules can be folded into a wide variety of shapes, which help determine how they function in cells. A software platform called Rosetta was invented at the UW more than a decade ago to analyze protein-folding patterns. Rosetta, along with a more recently developed program called HBNet, played a key role in designing new breeds of protein molecules that include additional hydrogen bonds.
In DNA molecules, hydrogen bonds are the key to an encoding system that involves four chemicals: adenine, thymine, guanine and cytosine. It’s hydrogen bonds that link adenine with thymine, and guanine with cytosine. The genomes of different organisms, from the lowliest microbe to us humans, consist of molecular strings like AGTCCGCGAATA … and so on.
The hydrogen-bond networks engineered into protein molecules “may provide the basis for a new generation of protein-based molecular structures of programmable shape, similar to DNA origami,” Ravit Netzer and Sarel Fleishman, biochemists at Israel’s Weizmann Institute of Science, wrote in a Science commentary. “Unlike DNA, however, these assemblies could be easily interfaced with proteins of desired function.”
UW biochemist Zibo Chen, a co-author of the study, said in an email that the challenge ahead will be to find a set of hydrogen-bond networks that could complement each other in a coding system. “Once we have a big set … one can think about having a lot of cool applications, like synthetic cell signaling pathways, programmable protein self-assembly, etc.,” he told GeekWire.
Scott Boyken of the University of Washington is the first author of the Science paper, titled “De Novo Design of Protein Homo-oligomers With Modular Hydrogen-Bond Network-Mediated Specificity.” In addition to Baker and Chen, other authors include Benjamin Groves, Robert Langan, Gustav Oberdorfer, Alex Ford, Jason Gilmore, Chunfu Xu, Frank DiMaio and Georg Seelig at the University of Washington; Jose Henrique Pereira of the University of Graz and the Joint BioEnergy Institute; and Banumathi Sankaran and Peter Zwart of Lawrence Berkeley National Laboratory.
Correction for 3:15 p.m. PT May 13: I’ve revised the item to reflect the fact that adenine, thymine, guanine and cytosine are nucleotides, not amino acids. Thanks to MarkW for pointing out the error.