The Impact of Protein Characterization

Proteins are involved in a vast number of functions, and understanding their behavior has undoubtedly become one of major focal points of scientific research today. Recently developed techniques for protein characterization and new purification methods allow us to analyze protein structure and comprehend these complex molecules in detail.

The early beginnings of protein characterization

Protein purification and characterization started over 200 years ago — the first attempts at isolating substances were reported in 1789. However, the techniques employed those days were very different from modern methods (1). Ovalbumin was the first crystalline protein obtained by the biochemist Hofmeister in 1889, but up until the 1940s, the isolation of this and other proteins from plants was only used for academic purposes, as protein structure was not fully understood (2). It was not until World War II, when proteins from serum became the subject of study for science. Since then, the development and implementation of more accurate technology has allowed researchers to thoroughly explore the infinite world of proteins. 

How do we study proteins?

The detection and purification of the protein and the characterization of its structure provide researchers with the information they need to analyze protein behavior and interaction with other molecules.

The primary conformation of a protein can be determined by using DNA sequencing techniques (3). These techniques aim to determine the exact order of the nucleotides in a strand of DNA.  However, to fully understand protein behavior, scientists must study the molecule after it suffers posttranslational modifications and acquires its three dimensional conformation. The three dimensional conformation is what actually defines protein function and may depend on the pH, temperature and other variables.

New and more sophisticated protein characterization tools allow for higher quality results, better aggregation prediction, and the monitoring of unfolding and developability for a vast number of proteins such as enzymes, biologics, and antibodies. Consistent and more accurate results are of great importance for scientists and doctors to make better decisions related to healthcare.

Why is protein characterization so important?

The study of biomolecules, known as proteomics, and involves protein characterization of their functions and purification methods (4). Proteomics constantly contribute to various  advances in biotechnology and medicine that base their treatments in the use of proteins. Some examples include:

– Enzymes: These were the first proteins of real interest for scientific research. Many  diseases and disorders can be related to a deficiency or misfolding of enzymes (5). Early detection of these anomalies, through protein characterization, has significantly improved the quality of modern disease treatments.

– Membrane proteins: these molecules play crucial roles in the regulation of ion transport across the membrane, chemical and electrical signaling in molecules, and mediation of cellular attachment. They also control cell membrane composition (6). Evidence supports that many diseases can be  related to alterations in the structure of membrane proteins, and protein characterization is crucial for predicting and treating these events.

– Hormones: Recombinant hormones are administered to patients with a detected deficiency in the synthesis of hormonal proteins.

– Antibodies: Being able to detect alterations in the structure of the antibodies in some patients, has given doctors the chance to utilize therapies that involve the administration of immunoglobulins.

Proteomics have not only become a great tool for the detection of many physiological disorders, but have also made an invaluable contribution toward the prediction of the activity and stability of pharmaceutical drugs. They have given health industry the confidence to develop better therapies and improve the lives of millions of patients.

References:

1. Overview of the Purification of Recombinant Proteins. Current Protocol Protein Sci. 2015; 80: 6.1.1–6.1.35.

Published online 2015 Apr 1. doi:  10.1002/0471140864.ps0601s80

2. Belitz H, Grosch W, Schieberle P. Food Chemistry. 4th edition. Springer. 2009.
3. Deutzmann R.  Structural characterization of proteins and peptides. Methods Mol Med. 2004;94:269-97.
4. Vaudel M, et al. Exploring the potential of public proteomics data. Proteomics. 2016 Jan; 16(2): 214–225. Published online 2015 Dec 15. doi:  10.1002/pmic.201500295
5. Gurung N, Ray S, Bose S, Ray V. A Broader View: Microbial Enzymes and Their Relevance in Industries, Medicine, and Beyond. Biomed Res Int. 2013; 2013: 329121. Published online 2013 Sep 11. doi:  10.1155/2013/329121
6. Pérez-Aguilar J, Saven J. Computational Design of Membrane Proteins. Structure. Author manuscript; available in PMC 2014 Jul 24. Published in final edited form as: Structure. 2012 Jan 11; 20(1): 5–14. doi:  10.1016/j.str.2011.12.003