Proteins are the molecular machines that make all living things buzz. They stop deadly infections, heal cells, capture energy from the sun, and more.
Proteins are built by linking together chemical building blocks called amino acids, according to the instructions of an organism’s genome. These strings then “bend” based on chemical forces between amino acids, forming the complex three-dimensional structures needed to perform specific tasks.
Fluorescent proteins have revolutionized our ability to study biological systems. Despite a multitude of fluorescence tools, some fundamental biological processes -; like interactions between proteins and metabolites -; remain difficult to study.
Assistant Professor Jeremy Mills and his group at Arizona State University’s School of Molecular Sciences and Biodesign Institute’s Center for Molecular Design and Biomimetics just published their research in the journal Biochemistry and present a new solution to this problem.
Specifically, they use a fluorescent amino acid that is not found in nature to generate a number of new fluorescent proteins whose light-emitting properties change when they interact with biotin, a very important compound in many. metabolic processes.
“An important aspect of this study is that atomic level images of many of these new proteins have been generated and provide a lot of information on how the binding of biotin alters the fluorescence properties of proteins,” said Mills. . “This information lays the groundwork for the development of new fluorescent proteins that will help deepen the legacy fluorescent proteins have already forged in the study of biological systems.”
Jeremy Mills’ protein studies are characterized by exceptional scholarship and an unwavering commitment to making critical advancements that will benefit science and society as a whole. “
Tijana Rajh, Director, School of Molecular Sciences
This study involved a huge amount of work, including designing protein constructs and experiments, and protein purification and crystallization in order to collect diffraction data. The data will be used in future studies aimed at the rational design of fluorescent sensors based on proteins binding or dissociating small molecules.
This work was funded by a grant from the National Institutes of Health (NIH). The Research Project Grant (R01) is the original and historically oldest grant mechanism used by the NIH. The objective of the grant is to develop new fluorescent protein-based tools that will be widely applicable to the study of biological systems in a way that would be very difficult to achieve using existing fluorescent proteins.
Although nature has been building proteins for over three billion years, the number of possible proteins is astronomical: there are more ways to put 100 amino acids together than there are atoms in the body. universe. For years, scientists have tried to predict what shapes protein molecules should take based on their amino acids -; with limited success. The current study is an important step towards understanding how to harness the power of proteins to help guide future efforts to rationally design new fluorescent sensors.
Mills is also passionate about bringing his enjoyment of science to the local community. He attributes much of his love of research to his participation in science fairs locally and internationally while in high school. He is a judge at the Arizona Science and Engineering Fair and the International Science and Engineering Fair when possible. He also frequently demonstrates the use of Foldit protein folding software to the public and has even developed lessons for a lay audience that uses Foldit as a basis.
Gleason, RP, et al. (2021) NEXT Structural origins of spectroscopic properties altered upon ligand binding in proteins containing a non-canonical fluorescent amino acid. Biochemistry. doi.org/10.1021/acs.biochem.1c00291.