Structural biology of innate immunity.
Innate immune responses depend on timely recognition of pathogenic or danger signals by multiple cell surface or cytoplasmic receptors and transmission of signals for proper counteractions through adaptor and effector molecules. At the forefront of innate immunity are four major signaling pathways, including those elicited by Toll-like receptors, RIG-I-like receptors, inflammasomes, or cGAS, each with its own cellular localization, ligand specificity, and signal relay mechanism. They collectively engage a number of overlapping signaling outcomes, such as NF-κB activation, interferon response, cytokine maturation, and cell death. Several proteins often assemble into a supramolecular complex to enable signal transduction and amplification. In this article, we review the recent progress in mechanistic delineation of proteins in these pathways, their structural features, modes of ligand recognition, conformational changes, and homo- and hetero-oligomeric interactions within the supramolecular complexes. Regardless of seemingly distinct interactions and mechanisms, the recurring themes appear to consist of autoinhibited resting-state receptors, ligand-induced conformational changes, and higher-order assemblies of activated receptors, adaptors, and signaling enzymes through conserved protein-protein interactions.
['Yin|Qian|Q|', 'Fu|Tian-Min|TM|', 'Li|Jixi|J|', 'Wu|Hao|H|']
D000818:Animals D006801:Humans D007113:Immunity, Innate D058847:Inflammasomes D008565:Membrane Proteins D011485:Protein Binding D051192:Receptors, Pattern Recognition D015398:Signal Transduction D013329:Structure-Activity Relationship
Toll-like receptor RIG-I-like receptor inflammasome cGAS higher-order assembly STING death domain superfamily