Directionally challenged proteins lead to eye and neurological disease
If a protein faces the wrong way, it could lead to eye and neurological diseases
New research shows that important proteins in the human body need to be positioned correctly at their workstation to do their job. Graduate student Duncan Boren was awarded the 2025 Keegstra and Thomashow Travel Award for this research.
Teaming up with international medical researchers, members of the Michigan State University-Department of Energy Plant Research Laboratory, or PRL, look at a human protein called cis-Prenyltransferase, or h-cisPT. This protein makes prenyl chains, building blocks essential to human health.
If this protein is mutated, it can cause eye or neurological disease. By understanding the ways these proteins work, researchers can help combat these health issues. This research was published in Protein Science.
“The most important part to this study was to figure out what face of the protein points towards the membrane when it interacts with the membrane as it makes prenyl chains,” said Josh Vermaas, assistant professor in the PRL and the Department of Biochemistry and Molecular Biology.
The h-cisPT protein builds prenyl chains by adding subunits, like links, onto the chain. The protein needs to be oriented correctly on the membrane surface to do its work, in a specific binding pose. By using computer simulations, the researchers identified this pose and the specific amino acids that stabilize the protein on the membrane surface. These critical contact sites are like the anchors that keep the protein from drifting away while it waits for more inputs.
The researchers are planning to keep looking into this protein, expanding to how related proteins function in plants, specifically in rubber trees, as the same chemical reaction is used in biology to make rubber.
“That is one of the things that got us interested in this, is that there is functional similarity to an interesting plant protein,” said Boren. “It's exciting to me. It's also economically significant. Rubber production is enormous industrially and it's kind of mysterious.”
Keegstra and Thomashow Travel Award
The Keegstra and Thomashow Travel Award is named for two former directors of the PRL, Kenneth Keegstra and Michael Thomashow. The award annually recognizes one or two distinguished PRL graduate students to enrich their graduate education and future careers.
Boren is a fourth-year graduate student in the Department of Biochemistry & Molecular Biology, or BMB, and Molecular Plant Sciences. He will use the award to present new research on membrane interactions at this year’s Gordon Research Conference for Natural Products.
“This gives me this opportunity to independently go to an exciting conference that otherwise it might be harder to go to,” Boren said. “The upshot is I get to present this specific, very interesting research that represents what I've most recently published. It's nice to be able to choose to go somewhere because it is interesting and feels fitting, instead of going somewhere because it is most convenient.”
Boren is mentored by Josh Vermaas, who nominated him for the award.
“Duncan has the intangibles to be a leading computational scientist both in the lab and as a community leader, translating advances in the laboratory for a broad audience,” Vermaas wrote in nominating Boren for the award. “Duncan's research goals are closely coupled to his own moral compass, seeking to eliminate hunger amid a warming climate, and I am confident [this] will lead him to future success.”
Funding for the portion of this research done at Michigan State University came from MSU’s Institute for Cyber-Enabled Research, the National Institute of General Medical Sciences of the National Institutes of Health and the Integrated training Model in Plant And Compu-Tational Sciences (IMPACTS) NSF-NRT training grant.
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