Understanding the molecular sociology of proteins
At some point during our education most of us learn some basic cell biology with cartoons of cells and organelles in text books, illustrating cellular organization. What is lost on most of is the fact that inside the cell is a molecular storm driven by the energy of the molecules themselves, far from what the simple textbook graphics of the cell would suggest.
You would think that life in a completely unrestricted space would quickly dissipate into a random soup of molecules in Brownian molecular motion. But surprisingly, it is the overwhelming force of the completely random molecular motion of water molecules that activate proteins and small molecules to cooperate and push them over their activation energy to form complexes or drive enzymatic reaction.
But this is not completely random! At the atomic level, this “complete randomness is restricted” for metabolites and proteins through cellular compartmentalization providing control for molecules in the cellular environment.
Like what you are learning?
Remember the days at school and the cliques that we may or may not have been part of? Molecular systems are just like this. Organelles, such as the cell nucleus provide the separation of specialized proteins from the rest of the cell to faithfully read and write genetic information, while mitochondria provides energy for the cell without affecting proteins in the remaining environment. Sometimes, proteins from other cliques interact with each other, and understanding how and where and with whom is the question of many biological research projects in cell biology.
Comprehending the ‘sociology of proteins’, the order, disorder and change of proteins within the cellular space has been elucidated in the past using high-resolution microscopy techniques. The images generated here are some of the most awe-inspiring pictures of the cellular environment . However, proteins can interact with many other proteins in the cell during their lifetime and the ‘social network’ of proteins is not illuminated through a simple image under a high-resolution microscope, often limited to four proteins associated with a particular color of a fluorescence label. A new, more powerful and quantitative technique is necessary to describe the dynamic picture of the cellular environment on a proteome-wide scale complementing the colorful images generated by high resolution microscopy techniques.
Dr. Christoforou and colleagues use quantitative proteomics to study protein localization at the level of the whole cell or of subcellular organelles [2016 Nature Communications paper ]. Separating a cell into its compartments and tagging each protein associated with a cellular compartment followed by high-resolution mass spectrometry provides insights into the ‘social order’ of proteins with proteome-wide coverage in a single experiment. For thousands of proteins, multiplexed proteomics techniques delivers the necessary information density to understand organelle residency, sub-organellar structure and the impact of protein isoforms on location and dynamic localization of proteins. With this new tool, we can now begin to understand the busy ‘social life’ of proteins with a cell-wide spatial coverage creating a new image of the cell – proteins that overcome the molecular storm interacting with other proteins to drive those fast-changing and subtle processes of life.
- See biological systems through space and time, using multiplexed proteomics
- Webinar: Robust classification of stem cell protein localization by SPS-MS3
- Video: Deepening Subcellular Proteomic Insights at Cambridge University with Mass Spectrometry
- Resource: TOP 10 Reasons to Use TMT10plex Multiplexing