8jyx

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

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:,
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).[1] [2]

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[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Daskalov A, Gladieux P, Heller J, Glass NL. Programmed Cell Death in Neurospora crassa Is Controlled by the Allorecognition Determinant rcd-1. Genetics. 2019 Dec;213(4):1387-1400. PMID:31636083 doi:10.1534/genetics.119.302617
  2. Daskalov A, Mitchell PS, Sandstrom A, Vance RE, Glass NL. Molecular characterization of a fungal gasdermin-like protein. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18600-18607. PMID:32703806 doi:10.1073/pnas.2004876117
  3. Li Y, Hou Y, Sun Q, Zeng H, Meng F, Tian X, He Q, Shao F, Ding J. Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms. Science. 2024 Apr 25:eadm9190. PMID:38662913 doi:10.1126/science.adm9190

8jyx, resolution 2.35Å

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