Proteins are fascinating molecular machines built from chains of amino acids. The ribosome is like a tiny factory that reads messenger RNA instructions to produce these protein chains. After the protein is formed, it folds into a specific shape due to interactions between its amino acids, which is crucial for its function.
While some proteins can do their job alone, many must form complexes with other proteins. These complexes are essential for carrying out a variety of biological tasks.
Protein complex formation is indeed a delicate and precise process. When proteins misfold or fail to find their partners, it can lead to severe cellular issues, resulting in diseases like Alzheimer’s or certain types of cancers.
For a long time, it was believed that proteins formed complexes only after they were completely synthesized. However, this new study has shown that many proteins start forming complexes while still being synthesized, a process known as co-translational assembly.
A study by the University of Geneva and collaborators found that protein assembly often starts during protein synthesis (or “birth”). This early assembly involves proteins that rely on each other for stability, much like a supportive couple.
This understanding can help develop new methods to fix assembly errors, which are linked to diseases like neurodegenerative disorders and certain cancers.
The team studies how proteins organize themselves, trying to find the basic rules for protein assembly. They looked at proteins that start assembling while being made (co-translational assembly) and compared them to those that assemble after they are fully formed. This helped them identify key differences between these two assembly methods.
Saurav Mallik, a researcher at the Weizmann Institute and co-first author of the study, said, “Our bioinformatics analyses revealed that proteins interacting with their partners while still being synthesized tend to be unstable when isolated. These proteins depend on their partners; if they do not find it, they will adopt the wrong shape and get degraded.”
Johannes Venezian and Arseniy Lobov, co-first authors of the study, said, “Using this approach, we developed a model based on a large corpus of structural data, using both experimentally determined structures and those predicted by the artificial intelligence software AlphaFold. Our model leveraged the structural properties of a complex to predict whether it is associated co- or post-translationally.”
Scientists found that in some proteins, the parts that allow them to bind with partners are exposed very early. This means they can start interacting with their partner proteins right after they emerge from the ribosome.
They confirmed these findings with experimental data on several proteins. According to Emmanuel Levy, this research helps us better understand how proteins assemble inside cells and shows how protein structure affects their synthesis.
Since many diseases, like neurodegenerative disorders and certain cancers, are caused by misfolded proteins or faulty complexes, understanding co-translational assembly could lead to new ways to prevent these errors and develop new treatments.
Journal Reference:
- Saurav Mallik, Johannes Venezian, Arseniy Labov et al. Structural determinants of co-translational protein complex assembly. Cell. DOI: 10.1016/j.cell.2024.11.013
Source: Tech Explorist
