Improved structure of mouse gasdermin D: a new blueprint for structure-based drug design.

Acta Crystallogr F Struct Biol Commun

OMass Therapeutics, Building 4000, Chancellor Court, John Smith Drive, Oxford Business Park, ARC, Oxford OX4 2GX, United Kingdom.

Published: October 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Gasdermin D (GSDMD) is a protein that has gained significant attention in recent years due to its crucial role in inflammatory cell death, particularly pyroptosis. Pyroptosis is a highly inflammatory form of programmed cell death that is triggered by various microbial infections and sterile inflammatory stimuli. GSDMD acts as an executioner molecule in this process, leading to the release of pro-inflammatory cytokines and amplifying the immune response. Here, we present a higher resolution, significantly improved apo crystal structure of the deposited mouse structure model that will be beneficial for structure-based drug-design approaches towards this important pharmacological target.

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2053230X25007149DOI Listing

Publication Analysis

Top Keywords

cell death
8
improved structure
4
structure mouse
4
mouse gasdermin
4
gasdermin blueprint
4
blueprint structure-based
4
structure-based drug
4
drug design
4
design gasdermin
4
gasdermin gsdmd
4

Similar Publications

Retinitis pigmentosa (RP) affects around 1 in 4000 individuals and represents approximately 25% of cases of vision loss in adults, through death of retinal rod and cone photoreceptor cells. It remains a largely untreatable disease, and research is needed to identify potential targets for therapy. Mutations in 94 different genes have been identified as causing RP, including AGBL5 which encodes the main deglutamylase that regulates and maintains functional levels of cilia tubulin glutamylation, which is essential to initiate ciliogenesis, maintain cilia stability and motility.

View Article and Find Full Text PDF

Engineering resistance genes against tomato brown rugose fruit virus.

Sci China Life Sci

September 2025

MOE Key Laboratory of Bioinformatics and Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Tomato brown rugose fruit virus (ToBRFV) overcomes all known tomato resistance genes, including the durable Tm-2, posing a serious threat to global tomato production. Here, we employed in vitro random mutagenesis to evolve the Tm-2 leucine-rich repeat (LRR) domain and screened ∼8,000 variants for gain-of-function mutants capable of recognizing the ToBRFV movement protein (MP) and triggering hypersensitive cell death. We identified five such mutants.

View Article and Find Full Text PDF

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and molecular state, across diverse Chinese cohorts.

View Article and Find Full Text PDF

Background: Docetaxel is the most common chemotherapy regimen for several neoplasms, including advanced OSCC (Oral Squamous Cell Carcinoma). Unfortunately, chemoresistance leads to relapse and adverse disease outcomes.

Methods: We performed CRISPR-based kinome screening to identify potential players of Docetaxel resistance.

View Article and Find Full Text PDF

Cell death in multiple sclerosis.

Cell Death Differ

September 2025

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive neurodegeneration. Although current disease-modifying therapies modulate peripheral autoimmune responses, they are insufficient to fully prevent tissue specific neuroinflammation and long-term neuronal and oligodendrocyte loss. Growing evidence implicates various regulated cell death (RCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, not only as downstream consequences of chronic inflammation, but also as active drivers of demyelination, axonal injury, and glial dysfunction in MS.

View Article and Find Full Text PDF