Every cell is a crime scene. There is a constant struggle between the criminals plotting to kill the cell and the detectives trying to prevent the crime. Triggering cell death requires strengthening the criminals while keeping a cell alive requires more detectives. Manipulating this crime for either side opens treatment options for various diseases such as cancer.
Apoptosis is a form of programmed cell death which appears to be a perfect crime. Killer proteins work together in a huge network to kill the cell and remove evidence resulting in one of our cells dying without us feeling it. Once this network is activated there is no way of stopping this so crime prevention by detective proteins has to occur early on. A dying cell can also protect the body if it became harmful, especially in cancer. This is why cancer cells often produce more detective proteins, finding and arresting any killer proteins. This stops one of the most effective defense mechanisms of the human body: the removal of harmful cells.
This study analyzes the details of an arrest: how a detective protein arrests a killer protein and keeps it locked up. But how to analyze something that small? Most structural methods require big complexes or a lot of material to analyze, which was not possible. Additionally, not only the proteins themselves but also their environment influences the network. The arrest can only take place at membranes limiting methods even more. Here, we introduced labels into both the detective and the killer protein which works similarly to a pinboard where all the evidence and hypotheses are collected. The "evidence" includes distances measured between the pins of the detective and the killer and analysis of their surroundings. Processing the evidence leads to a reconstruction of what the arrest actually looks like.
The detective protein chains itself to one part of the killer protein using a specific lock-mechanism. Even though, the rest of the killer can freely move, it is not able to escape like when a detective handcuffs a criminal to themselves to prevent their escape. Being able to precisely characterize which part of the detective functions as a lock makes it possible to design a lock pick and therefore precisely manipulate the lock in case of a mal function.
However, there are a lot of different killers and detectives in cells. Understanding one lock mechanism is a starting point but further mechanisms need to be analyzed to precisely kill cancer cells with as little side effects as possible.
Editor: Massimo Caine
