The SCHOOL of nature: I. Transmembrane signaling.

Abstract

Receptor-mediated transmembrane signaling plays an important role in health and disease. Recent significant advances in our understanding of the molecular mechanisms linking ligand binding to receptor activation revealed previously unrecognized striking similarities in the basic structural principles of function of numerous cell surface receptors. In this work, I demonstrate that the Signaling Chain Homooligomerization (SCHOOL)-based mechanism represents a general biological mechanism of transmembrane signal transduction mediated by a variety of functionally unrelated single- and multichain activating receptors. within the SCHOOL platform, ligand binding-induced receptor clustering is translated across the membrane into protein oligomerization in cytoplasmic milieu. This platform resolves a long-standing puzzle in transmembrane signal transduction and reveals the major driving forces coupling recognition and activation functions at the level of protein-protein interactions-biochemical processes that can be influenced and controlled. The basic principles of transmembrane signaling learned from the SCHOOL model can be used in different fields of immunology, virology, molecular and cell biology and others to describe, explain and predict various phenomena and processes mediated by a variety of functionally diverse and unrelated receptors. Beyond providing novel perspectives for fundamental research, the platform opens new avenues for drug discovery and development.