Proteins are large biomolecules that are an integral part of a wide range of functions in all living organisms. Their ever-changing structure and role in the different metabolic pathways are, and have been, an area of intense study for many years. Understanding their interactions with other proteins and molecules is of high relevance for drug design and the development of medical treatments.
Protein Structure Explained
Proteins are macromolecules made of amino acids, organic compounds that combine forming chains called polypeptides. These chains shape the structure and determine the configuration of each protein. Proteins differ from one another in their sequence of amino acids, and the genes in our DNA contain the information for the coding of that chain. Once they are synthesized, proteins fold and acquire a three-dimensional structure that will dictate the activity they will carry out in the human body. For this reason, understanding how each protein’s primary structure is naturally and sequentially formed, helps researchers to elucidate the role of each protein.
Abnormal or misfolded proteins are considered unstable and are degraded more rapidly by the cell. Many diseases are related to the permanent alteration or loss of function in proteins generally caused by defective genes. Importantly, the aggregation and misfolding of individual vulnerable proteins influence not only their own structural folding, but that of others sharing common pathways, which leads to disease (1). Therefore, it is important for researchers to fully and accurately understand protein structure and their behaviour in their correspondent network so that they may properly develop disease treatment.
Many treatment drugs are synthesized in the laboratory to replace unstable abnormal proteins. Others work as inhibitors or trigger signaling in a defectuous network due to loss of activity from misfolded proteins. New and more accurate techniques like nanoDSF, are allowing researchers to better understand the stability of proteins. This inexpensive and efficient research method monitors the thermal transitions of proteins, such as protein unfolding, in the presence of a fluorescent dye; providing quick results. Such tools give medical laboratories the ability to easily analyze protein structures, aiding in the design and production of more specific disease treatments. Proper analysis comes from understanding and characterizing protein functions and interactions.
Functions and Interactions
Included in their wide array of functions, proteins are catalysts for nearly 4000 metabolic reactions: they orchestrate DNA replication, form part of the cell structure, operate as receptors, are part of the immune system, and act as transport molecules. Because proteins are not entirely rigid molecules, they generally change their structure and often form bonds while interacting with other proteins or molecules, called ligands (3). One example of this binding is haemoglobin, a protein that binds to oxygen and is responsible for its transportation to other cells. A stable structure is crucial if proteins are to keep their chemical properties and bind specifically to form these type of complexes.
Protein–protein interactions are involved in enzymatic activity regulation, dictating cell functions, carrying out biological processes, and are part of a complex signaling network that triggers or inhibits a universe of actions in the organism (4). Without a complex knowledge of these interactions and how they affect protein structure, disease treatment and drug development would be next to impossible.
Our cells are continuously producing proteins and, as we age, they become more susceptible to mutations that can cause disease. Our body naturally tries to fix or degrade defectuous molecules but in many cases it fails. Utilizing techniques to study and characterize proteins can help researchers monitor structural changes and affected interactions to better understand these protein deficiencies and develop proper disease treatment drugs.
1. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE 2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem 78: 23.21–23.33
2. Bairoch A. The ENZYME database in 2000. Nucleic Acids Research. 28 (1): 304–305. PMC 102465 . PMID 10592255. doi:10.1093/nar/28.1.304. Archived from the original on June 1, 2011.
3. Teif Vladimir. Ligand-Induced DNA Condensation: Choosing the Model. Biophys J. 2005 Oct; 89(4): 2574–2587.
Published online 2005 Aug 5. doi: 10.1529/biophysj.105.063909
4. Mathews K,, Van Holde E., Appling D., Anthony Cahill J. Biochemistry (4th Edition). Ed: Addison-Wesley. 2013.