This week we feature Editor’s Picks by Sephorah Zaman, PhD., a Science Editor for JoVE's Neuroscience section. Before JoVE, Dr. Zaman worked as a postdoc in a neuroscience lab at Columbia University.
Dr. Zaman: It is a widely accepted notion in biology that the structure of bio-molecules usually affects their function. Proteins are no exception. However, when a protein is made, it exists in linear form with no particular shape. In order to perform its function, the protein must fold into a very precise three-dimensional structure. The protein folding phenomenon has fascinated me ever since when I was an undergrad I read that out of an almost infinite number of possibilities, the protein must fold into the one correct three-dimensional structure that allows it to perform its function. Further, improperly folded proteins can lead to many human diseases ranging from allergies to Alzheimer's. Thus, protein folding is a vital area of research.
Pick 1 — "Analyzing Protein Dynamics Using Hydrogen Exchange Mass Spectrometry"
Dr. Zaman: To understand how this technique works, think about a ball of wool that has been placed in colored dye. Afterward, if you unravel the yarn, some parts of the wool will be colored and some wont, because parts of it (that are on the inside) were protected from the dye due to the structure of the yarn. If the shape of the yarn changes, then the pattern of protection will change. Using biochemical methods, the authors in this video analyze protection from deuteron incorporation to understand how proteins fold, unfold and respond to their environment. I really like this video because it describes the entire experimental procedure from prepping the samples to data analysis and also includes troubleshooting tips.
Dr. Zaman: When a protein does not fold correctly, it often loses its function. For example, if a protein required for motility is misfolded, then the results could be paralysis. In this video, the authors use behavioral assays in an intact animal as an indicator of protein misfolding. This approach is different because protein misfolding assays are traditionally done in vitro. Further, incorrectly folded proteins often do not end up in the right place in the cell. The authors use fluorescently labeled proteins to track misfolded proteins within the cell. Finally, sensitivity to protease (an enzyme that cleaves peptide bonds) is used to detect structural changes in the protein itself. In this way, this video looks at protein folding at three levels — at the molecular and cellular levels and at the level of the organism.
Pick 3 — "Rapid Generation of Amyloid from Native Proteins In vitro"
Dr. Zaman: In this video article, the authors describe a relatively straightforward technique to convert a protein into an amyloid. Amyloids are insoluble protein aggregates that share a common structure and have been implicated in many human diseases such as Parkinson’s. Being able to prepare amyloid from a protein is important because after preparing the amyloid, its characteristics can be determined leading to potentially clinical applications. For me, being able to see the applications of a technique are important because that it is what ultimately leads to an improvement in the quality of life.
Pick 4 — "Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides"
Dr. Zaman: Here we come back to the basic question of what forces govern protein self-assembly. This study looks at how short stretches of amino acids, termed peptides, spontaneously self-assemble into ordered structures. The authors show how two peptides self-assemble to form structures that look like "beaded necklaces." I like this video because understanding how these molecular building blocks assemble not only furthers our understanding of the basic science behind the process but can also have applications in materials science, such as in developing vehicles for drug delivery.