Structural highlights
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
- ↑ 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
- ↑ 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
- ↑ 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
