Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3.
Journal, issue, pages	Nature, Vol. 604, Issue 7904, Page 184-189, Year 2022
Publish date	Feb 3, 2022
Authors	Inga V Hochheiser / Michael Pilsl / Gregor Hagelueken / Jonas Moecking / Michael Marleaux / Rebecca Brinkschulte / Eicke Latz / Christoph Engel / Matthias Geyer /
PubMed Abstract	NLRP3 is an intracellular sensor protein that when activated by a broad spectrum of exogenous and endogenous stimuli leads to inflammasome formation and pyroptosis. The conformational states of NLRP3 ...NLRP3 is an intracellular sensor protein that when activated by a broad spectrum of exogenous and endogenous stimuli leads to inflammasome formation and pyroptosis. The conformational states of NLRP3 and the way antagonistic small molecules act at the molecular level remain poorly understood. Here we report the cryo-electron microscopy structures of full-length human NLRP3 in its native form and complexed with the inhibitor CRID3 (also named MCC950). Inactive, ADP-bound NLRP3 is a decamer composed of homodimers of intertwined leucine-rich repeat (LRR) domains that assemble back-to-back as pentamers. The NACHT domain is located at the apical axis of this spherical structure. One pyrin domain dimer is in addition formed inside the LRR cage. Molecular contacts between the concave sites of two opposing LRR domains are mediated by an acidic loop that extends from an LRR transition segment. Binding of CRID3 considerably stabilizes the NACHT and LRR domains relative to each other. CRID3 binds into a cleft, connecting four subdomains of the NACHT with the transition LRR. Its central sulfonylurea group interacts with the Walker A motif of the NLRP3 nucleotide-binding domain and is sandwiched between two arginine residues, which explains the specificity of NLRP3 for this chemical entity. With the determination of the binding site of this key therapeutic agent, specific targeting of NLRP3 for the treatment of autoinflammatory and autoimmune diseases and rational drug optimization is within reach.
External links	Nature / PubMed:35114687
Methods	EM (single particle)
Resolution	3.84 - 9.6 Å
Structure data	EMDB-13684: Multibody refined monomer of the human NLRP3 decamer assembly. Method: EM (single particle) / Resolution: 4.8 Å EMDB-13685: Focussed refinement of a NACHT domain of the human NLRP3 decamer. Method: EM (single particle) / Resolution: 4.1 Å 13686 7pzc EMDB-13686: High resolution reconstruction of the human NLRP3 decamer PDB-7pzc: Cryo-EM structure of the NLRP3 decamer bound to the inhibitor CRID3 Method: EM (single particle) / Resolution: 3.9 Å EMDB-13687: Reconstruction of the apo state of the human NLRP3 decamer. Method: EM (single particle) / Resolution: 9.6 Å EMDB-13692: Reconstruction of the human NLRP3 decamer with well-defined acidic loop Method: EM (single particle) / Resolution: 8.0 Å EMDB-13693: Reconstruction of the human NLRP3 decamer in D5 symmetry. Method: EM (single particle) / Resolution: 3.84 Å EMDB-13699: Reconstruction of the human NLRP3 decamer in C1 symmetry Method: EM (single particle) / Resolution: 6.3 Å
Chemicals	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-8GI*: 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-urea
Source	homo sapiens (human)
Keywords	IMMUNE SYSTEM / NLRP3 / CP-456.773 / CRID3 / MCC950 / AAA+ ATPase / NOD-like receptor / inflammasome