What is it about?
Gasdermin D (GSDMD) is a protein that has gained significant attention in recent years due to its vital role in inflammatory cell death, particularly in a process known as pyroptosis. Pyroptosis is a highly inflammatory form of programmed cell death that can be triggered by various microbial infections as well as sterile inflammatory stimuli. GSDMD serves as an executioner molecule in this process, leading to the release of pro-inflammatory cytokines and enhancing the immune response. This article discusses the higher resolution data, improved refinement statistics, and additional structural details that were unresolved in the previously deposited model of mouse GSDMD.
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Why is it important?
This study delivers the most accurate structure to date of mGSDMD, a protein that drives inflammatory cell death. When overactive, GSDMD contributes to serious diseases like sepsis and autoimmune disorders. By resolving previously unclear regions of the protein, especially the part that forms damaging pores in cell membranes, the new structure provides a precise blueprint for designing drugs that can block this process. This structure makes it easier to identify and develop new medicines that could control harmful inflammation and improve patient outcomes.
Perspectives
The availability of this improved structure opens several promising avenues. First, it provides a robust template for designing small molecules that stabilise mGSDMD in its inactive state, preventing pore formation and uncontrolled inflammation. Secondly, it creates opportunities to explore species-specific differences between mouse and human Gasdermin D, which is crucial for translating preclinical findings into human therapies.
Luigi De Colibus
IOM
Read the Original
This page is a summary of: Improved structure of mouse gasdermin D: a new blueprint for structure-based drug design, Acta Crystallographica Section F Structural Biology Communications, September 2025, International Union of Crystallography,
DOI: 10.1107/s2053230x25007149.
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