Study of Evolution of Thousands of Bacterial Proteins Allows Deciphering of Many Interactions Between Human Proteins

Cells operate like an incredibly well-synchronized orchestra of molecular interactions among proteins. Understanding this molecular network is essential not only to understand how an organism works but also to determine the molecular mechanisms responsible for a multitude of diseases. In fact, it has been observed that protein interacting regions are preferentially mutated in tumors. The investigation of many of these protein interactions is challenging. However, a study coordinated by Dr. Simone Marsili and Dr. David Juan, from Dr. Alfonso Valencia's team at the CNIO (Spain’s National Center for Oncological Investigations), should advance our knowledge on thousands of them. The work, published online on December 13, 2016 in PNAS, demonstrates that it is possible to understand a significant number of interactions among human proteins from the evolution of their counterparts in simpler cells, such as bacteria cells. The open-access PNAS article is titled “Conservation of Coevolving Protein Interfaces Bridges Prokaryote–Eukaryote Homologies in the Twilight Zone.” According to Dr. Rodríguez, from the Structural Computational Biology Group at the CNIO and first author of the paper, "the complexity of human beings does not only result from the number of proteins that we have, but primarily from how they interact with each other. However, out of 200,000 protein-protein interactions estimated, only a few thousand have been characterized at the molecular level". It is very difficult to study the molecular properties of many important interactions without reliable structural information. It is this "twilight zone" that, for the first time, CNIO researchers have managed to explore.
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