8jyx

Crystal structure of the gasdermin-like protein RCD-1-1 from Neurospora crassa

spinqualitylabelsall models 8jyx, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jyx is a 2 chain structure with sequence from Escherichia coli and Neurospora crassa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: GLC, PRD_900001 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RCD11_NEUCR Gasdermin-like protein involved in heterokaryon incompatibility, a process that ensures that during spontaneous vegetative cell fusion, only compatible cells from the same colony survive (non-self-recognition) (PubMed:31636083, PubMed:32703806). In N.crassa, the rcd-1 locus exists as 2 incompatible alleles, rcd-1-1 (this entry) and rcd-1-2 (AC P0DW10) (PubMed:31636083). During the allorecognition process, forms a heterooligomer with rcd-1-2, thereby forming a functional gasdermin-like complex that binds to membranes and forms pores, triggering cell death (PubMed:32703806). Binds negatively charged phospholipids, such as cardiolipin and phosphatidylserine (PubMed:32703806). Also binds to phosphoinositides, preferentially to phosphatidylinositol-3-phosphate (PtdIns-3-P), PtdIns-5-P and PtdIns-3,5-P2 (PubMed:32703806). Publication Abstract from PubMed Gasdermins (GSDMs) are pore-forming proteins that execute pyroptosis for immune defense. GSDMs are two-domain proteins, activated by proteolytic removal of the inhibitory domain. Here we report two types of cleavage-independent GSDM activation. First, TrichoGSDM, a pore-forming-domain-only protein from the basal metazoan Trichoplax adhaerens, is a disulfides-linked autoinhibited dimer, activated by reduction of the disulfides. Cryo-electron microscopy (cryo-EM) structure illustrates assembly mechanism for the 44-mer TrichoGSDM pore. Second, RCD-1-1/RCD-1-2, encoded by polymorphic rcd-1 in filamentous fungus Neurospora crassa, are also pore-forming-domain-only GSDMs. RCD-1-1 and RCD-1-2, when encountering each other, form pores and cause pyroptosis, underlying allorecognition in Neurospora. Cryo-EM structure reveals a pore of 11 RCD-1-1/RCD-1-2 heterodimers and heterodimerization-triggered pore assembly mechanism. This study shows mechanistic diversities in GSDM activation and indicates versatile functions of GSDMs. Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.,Li Y, Hou Y, Sun Q, Zeng H, Meng F, Tian X, He Q, Shao F, Ding J Science. 2024 Apr 25:eadm9190. doi: 10.1126/science.adm9190. PMID:38662913 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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