Unveiling the Complex Interactions of Immune Proteins: A New Frontier in Disease Therapy

Researchers delving into the microscopic functions of cells have uncovered the mechanisms by which immune system proteins collaborate to initiate an immune response. Acknowledgment: Jagannath Maharana/IIT Kanpur

High-resolution imaging elucidates the complex behavior of essential receptors, presenting new possibilities for disease intervention.

In the complex choreography of the body’s defense mechanisms against pathogenic intruders, specific proteins within the immune system hold central roles. Recent investigations conducted by the Bridge Institute at the USC Michelson Center for Convergent Bioscience, in association with global research partners from India, Australia, and Switzerland, have provided new clarity on these proteins.

This research potentially lays the groundwork for novel therapeutic approaches targeting a variety of diseases, encompassing severe manifestations of COVID-19, rheumatoid arthritis, neurodegenerative disorders, and cancer.

The Role of the Complement Cascade and Associated Receptors

At the core of our immunological response is the complement cascade, a sequence of events triggered when potential hazards are identified. This chain reaction gives rise to protein messengers, specifically C3a and C5a, which subsequently activate particular receptors on cells, thereby initiating a series of internal signaling pathways. The exact functions of these receptors, particularly the enigmatic C5aR1, have been largely elusive.

Employing cutting-edge cryo-electron microscopy (cryo-EM) technology, the scientists obtained in-depth images of these receptors as they operate. These images disclose how the receptors engage with molecules, undergo conformational changes upon activation, and relay signals within the cell.

Research Implications and Prospects for the Future

Cornelius Gati, the study’s principal investigator and assistant professor of biological sciences, chemistry, and quantitative and computational biology at the USC Dornsife College of Letters, Arts and Sciences, commented on the study, stating, “This research delivers extensive and significant insights into a key receptor family within the immune system.”

The discoveries made in this study indicate potential paths for the creation of pharmacological agents aimed at these receptors for the treatment of multiple diseases, noted Gati, who oversees USC’s cryo-EM facility, accessible to researchers worldwide.

As the international community faces ongoing challenges from diseases affecting millions, a deeper understanding of our immune system’s intricacies becomes increasingly vital. Published in the scientific journal Cell on October 17, this study adds to that knowledge base, serving as a foundational resource for subsequent research endeavors aiming to leverage the capabilities of our body’s innate defenses.

Reference Information

The paper was authored by 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 Mohapatra, 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. The paper was published in Cell with DOI: 10.1016/j.cell.2023.09.020.

Frequently Asked Questions (FAQs) about Immune System Proteins

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• Original Research Publication in Cell Journal
• Bridge Institute at the USC Michelson Center for Convergent Bioscience
• Cryo-Electron Microscopy Overview
• Complement Cascade Explained
• Information on Immune System Proteins
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• Introduction to Rheumatoid Arthritis
• Overview of Neurodegenerative Diseases
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