December 9, 2023

Using artificial intelligence, researchers have created the first map of a group of proteins called the commander complex, which act as the body’s “postman.” The new understanding opens the door to new medicines and ways to treat everything from Alzheimer’s to infectious diseases to cancer.

The 16-strong group of proteins found throughout the body is known as the commander complex, and it is involved in a myriad of biological functions, including boosting our immune response, maintaining homeostasis within cells, and working as a delivery and routing system.

“Just as the postal system has processes for transporting and sorting goods, the cells in our bodies have molecular machines for transporting and sorting proteins,” said Professor Brett Collins of the University of Queensland in Australia. “Cargo delivery is all about getting the right package to the right destination at the right time, and in the cell, the commander complex controls this system to make sure the right amount of protein gets to the right place.”

The complex has also been linked to a variety of diseases, including viruses, certain types of cancer, neurodegenerative diseases, atherosclerosis and Wilson’s disease, which interferes with the body’s ability to get rid of excess copper.

“Viruses such as SARS-CoV-2, which causes COVID-19, and human papillomavirus (HPV), which can cause cancer, require the Commander complex to infect cells, and it is involved in the trafficking of amyloid protein in Alzheimer’s disease,” Collins explain. “Mutations in the commander complex disrupt the transport of lipids into cells, leading to high cholesterol and heart defects in people with the rare Ritscher-Schinzel syndrome, which is characterized by intellectual disability and developmental delay.”

Understanding the ubiquity of this complex, Professors Collins and Pete Cullen of the University of Bristol, UK, led a team that set out to map its structure. Using new electron microscopy and various other imaging techniques, as well as machine learning, the project resulted in the first fully mapped visualization of all 16 proteins bound in the complex. With this map in hand, the researchers believe other scientists can get busy understanding how the Commander complex is linked to many diseases and, more importantly, how to combat its harmful effects.

“Understanding the 3D shape of these proteins helps us understand their function, why mutations cause disease, and how to design drugs that target them in the future,” Collins said.

One of the findings showed that all the proteins in the commander complex work together to carry out their activities. The findings, the researchers say, could mean that previous studies that focused on the role of individual proteins — including those conducted by the same team — need to be reexamined.

The research has been published in the journal cell.

You can check out the newly imaged Commander complex in the video below.

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Assembly of the Commander Complex 3D model

source: Simex