Secrets of Immune System Proteins: Unlocking Innovative Disease Treatments

Anaphylatoxin Recognition

Researchers peering into the minute workings of cells reveal how immune system proteins interact to mount an immune response. Credit: Jagannath Maharana/IIT Kanpur

Detailed imaging reveals intricate workings of key receptors, offering fresh insights into combating disease.

In the intricate dance of our body’s defenses against harmful invaders, certain immune system proteins play pivotal roles. New research from the Bridge Institute at the USC Michelson Center for Convergent Bioscience, in collaboration with international teams from India, Australia, and Switzerland, has shed light on these proteins.

The work potentially paves the way for innovative treatments for a range of diseases, including severe cases of COVID-19, rheumatoid arthritis, neurodegenerative diseases, and cancer.

The Complement Cascade and Its Receptors

Central to our immune response is the complement cascade, a series of events activated when potential threats are detected. This process produces protein messengers, C3a and C5a, which in turn activate specific receptors on cells, setting off a cascade of internal signals. The precise mechanisms of these receptors, especially the elusive C5aR1, have remained a mystery.

Using the advanced technique of cryo-electron microscopy (cryo-EM), the researchers captured detailed images of these receptors in action. These images unveil how the receptors interact with molecules, change shape upon activation, and transmit signals within the cell.

Research Insights and Future Potential

The study’s lead author, Cornelius Gati, assistant professor of biological sciences, chemistry, and quantitative and computational biology at the USC Dornsife College of Letters, Arts and Sciences, remarked on the findings, noting, “This research offers significant and comprehensive insights into a crucial receptor family within the immune system.”

The study’s revelations suggest potential avenues for the development of drugs targeting these receptors to treat various diseases, added Gati, who heads USC’s cryo-EM facility, which is available for use by researchers around the globe.

As the global community continues to grapple with diseases that impact millions, understanding the nuances of our immune system becomes ever more critical. This research, published in the journal Cell on October 17, contributes to that understanding, providing a foundation for future studies aiming to harness the power of our body’s natural defenses.

Reference: “Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors” by Manish K. Yadav, Jagannath Maharana, Ravi Yadav, Shirsha Saha, Parishmita Sarma, Chahat Soni, Vinay Singh, Sayantan Saha, Manisankar Ganguly, Xaria X. Li, Samanwita Mohapatra, Sudha Mishra, Htet A. Khant, Mohamed Chami, Trent M. Woodruff, Ramanuj Banerjee, Arun K. Shukla and Cornelius Gati, 17 October 2023, Cell.
DOI: 10.1016/j.cell.2023.09.020

Authors on the study include Gati and Postdoctoral Fellow Ravi Yadav of USC Dornsife’s Department of Molecular and Computational Biology; Htet Khant of USC Viterbi School of Engineering; Manish Yadav, Jagannath Maharana, Shirsha Saha, Parishmita Sarma, Chahat Soni, Vinay Singh, Sayantan Saha, Manisankar Ganguly, Samanwita Mahapatra, Sudha Mishra, Ramanuj Banerjee and Arun Shukla of the Indian Institute of Technology; Xaria Li and Trent Woodruff of the University of Queensland; and Mohamed Chami of Universität Basel.

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