Proteins, the molecular machines, make all living organisms hum. They are capable of healing cells, preventing deadly infections, trapping energy from the sun, and much more.
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Proteins are formed by attaching chemical building blocks named amino acids, based on instructions in an organism’s genome. These strings then “fold-up” depending on the chemical forces between the amino acids, resulting in complex three-dimensional structures required to carry out specific jobs.
The research on biological systems is revolutionized with fluorescent proteins. However, in spite of numerous fluorescence tools, certain fundamental biological mechanisms—like the interactions between proteins and metabolites—continue to remain tough to analyze.
Assistant Professor Jeremy Mills and his team from the Arizona State University’s School of Molecular Sciences and the Center for Molecular Design and Biomimetics in the Biodesign Institute have illustrated a new solution to this crisis. The study has been published in the journal Biochemistry.
The researchers employed a fluorescent amino acid that is not found in nature to create numerous novel fluorescent proteins whose light-emitting properties alter when interacting with biotin—a vital compound of numerous metabolic processes.
An important aspect of this study is that atomic-level pictures of many of these new proteins were generated that provide a great deal of information about how the binding of biotin changes the fluorescence properties of the proteins. This information lays a foundation for the development of new fluorescent proteins that will help further the legacy that fluorescent proteins have already forged in the study of biological systems.”
Jeremy Mills, Assistant Professor, School of Molecular Sciences, Arizona State University
Tijana Rajh, director of the School of Molecular Sciences, remarks, “The protein studies of Jeremy Mills are typified by outstanding scholarship and a relentless commitment to making critical advances that will benefit science and society at large.”
The research involved massive work. It included designing protein constructs and experiments, and purifying and crystallizing the proteins to gather diffraction data. The data can be employed for future research works aiming at the rational design of fluorescent, protein-based sensors of small molecule association or dissociation.
The current research was funded by a grant from the National Institutes of Health (NIH). The Research Project Grant (R01) is the original and historically oldest grant process used by NIH. The grant aims at creating new fluorescent, protein-based tools that can be widely applied to the analysis of biological systems in ways hard to achieve employing prevailing fluorescent proteins.
Nature is building proteins for more than three billion years and the number of likely proteins is astronomical. There are numerous ways in which 100 amino acids can be assembled than atoms in the universe.
Researchers, for a long time, have attempted to foretell the shapes of protein molecules depending on their amino acids—with little success. The recent research is an important step towards the understanding of utilizing the power of proteins to lead future activities to rationally design novel fluorescent sensors.
Gleason, P. R., et al. (2021) Structural Origins of Altered Spectroscopic Properties upon Ligand Binding in Proteins Containing a Fluorescent Noncanonical Amino Acid. Biochemistry. doi.org/10.1021/acs.biochem.1c00291.