8gnj

Human SARM1 bounded with NMN and Nanobody-C6, Conformation 2

spinqualitylabelsall models 8gnj, resolution 3.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gnj is a 3 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.78Å Ligands: NMN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Sterile alpha (SAM) and Toll/interleukin-1 receptor (TIR) motif containing 1 (SARM1) is an autoinhibitory NAD-consuming enzyme that is activated by the accumulation of nicotinamide mononucleotide (NMN) during axonal injury. Its activation mechanism is not fully understood. Here, we generate a nanobody, Nb-C6, that specifically recognizes NMN-activated SARM1. Nb-C6 stains only the activated SARM1 in cells stimulated with CZ-48, a permeant mimetic of NMN, and partially activates SARM1 in vitro and in cells. Cryo-EM of NMN/SARM1/Nb-C6 complex shows an octameric structure with ARM domains bending significantly inward and swinging out together with TIR domains. Nb-C6 binds to SAM domain of the activated SARM1 and stabilized its ARM domain. Mass spectrometry analyses indicate that the activated SARM1 in solution is highly dynamic and that the neighboring TIRs form transient dimers via the surface close to one BB loop. We show that Nb-C6 is a valuable tool for studies of SARM1 activation. A conformation-specific nanobody targeting the nicotinamide mononucleotide-activated state of SARM1.,Hou YN, Cai Y, Li WH, He WM, Zhao ZY, Zhu WJ, Wang Q, Mai X, Liu J, Lee HC, Stjepanovic G, Zhang H, Zhao YJ Nat Commun. 2022 Dec 22;13(1):7898. doi: 10.1038/s41467-022-35581-y. PMID:36550129 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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