First map of "Commander complex" could help fight diseases, dementia
Using AI, researchers have created the first map of a group of proteins known as the Commander complex, which function as the body's "postal workers." The new understanding opens the door to new drugs and modalities for fighting everything from Alzheimer's to infectious diseases to cancer.
Found throughout the human body, the 16-strong protein group called the Commander complex is involved with myriad biological functions including mounting our immune response, maintaining homeostasis in cells, and working as sort of a delivery and routing system.
“Just as the postal system has processes to transport and sort cargo, cells in our bodies have molecular machines that transport and sort proteins,” said Prof. Brett Collins from the University of Queensland in Australia. “Cargo transport is all about getting the right parcels to the right destination at the right time and in cells, the Commander complex controls this system to ensure the right amount of protein is delivered to the right place.”
The complex has also been linked to multiple diseases including viruses, certain types of cancer, neurodegenerative conditions, atherosclerosis, and Wilson's disease, which interferes with the body's ability to get rid of extra copper.
“Viruses such as SARS-CoV-2 – which causes COVID-19 – and human papilloma virus (HPV) which can lead to cancer, need the Commander complex to infect cells, and it has been linked to the transport of the amyloid protein in Alzheimer’s disease," said Collins. “Mutations in the Commander complex disrupt the transport of lipids into cells, causing high cholesterol and heart defects in people with the rare Ritscher-Schinzel syndrome which is characterized by intellectual disability and development delay."
Understanding the ubiquitous nature of the complex, Collins and Prof. Pete Cullen from the University of Bristol in England, led a team that set out to map its structure. Using new electron microscopy and a variety of other imaging techniques along with machine learning, the project led to the first fully mapped visualization of all 16 proteins bound in the complex. Armed with this map, the researchers believe that other scientists can get busy learning just how the Commander complex is implicated in many diseases and, more importantly, how to fight its deleterious effects.
“Knowing the 3D shape of these proteins helps us understand how they function, why mutations cause disease, and how to design drugs to target them in the future,” Collins said.
One of the findings from the studies showed that all of the proteins in the Commander complex act together to carry out its activities. This discovery, say the researchers, may mean that previous studies focusing on the actions of the individual proteins – including one carried out by the same team – need to be reexamined.
The study has been published in the journal Cell.
You can view the newly imaged Commander complex in the video below.
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