6pxr

Anti-TAU BIIB092 FAB with TAU peptide

spinqualitylabelsall models 6pxr, resolution 1.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pxr is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.556Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A2NHM3_MOUSE Publication Abstract from PubMed Deposition of tau aggregates in the brain is a pathological hallmark of several neurodegenerative diseases, termed tauopathies, such as Alzheimer's disease (AD), corticobasal degeneration, and progressive supranuclear palsy (PSP). As transcellular spread of pathological tau aggregates has been implicated in disease progression, immunotherapy is being considered as a treatment for tauopathies. Here we report a detailed biochemical and biophysical characterization of the tau-binding properties of gosuranemab, a humanized monoclonal antibody directed against N-terminal tau that is currently being investigated as a treatment for AD. Binding experiments showed that gosuranemab exhibited high affinity for tau monomer, tau fibrils, and insoluble tau from different tauopathies. Epitope mapping studies conducted using X-ray crystallography and mutagenesis showed that gosuranemab bound to human tau residues 15-22. Immunodepletion of pathological human brain homogenates and transgenic mouse interstitial fluid (ISF) with gosuranemab resulted in reduced tau aggregation in tau biosensor cells. Preincubation of seed-competent AD-tau with gosuranemab significantly inhibited tau aggregation in mouse primary cortical neurons. Gosuranemab also significantly reduced unbound N-terminal tau in cerebrospinal fluid (CSF) from individuals with PSP and AD, and in ISF and CSF of treated transgenic mice. These results are consistent with the >90% target engagement observed in the CSF of some clinical trial dosing cohorts and support the evaluation of gosuranemab as a potential treatment for AD. Characterization of tau binding by gosuranemab.,Sopko R, Golonzhka O, Arndt J, Quan C, Czerkowicz J, Cameron A, Smith B, Murugesan Y, Gibbons G, Kim SJ, Trojanowski JQ, Lee VMY, Brunden KR, Graham DL, Weinreb PH, Hering H Neurobiol Dis. 2020 Dec;146:105120. doi: 10.1016/j.nbd.2020.105120. Epub 2020 Sep , 28. PMID:32991997 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Microtubule-associated protein 3D structures Monoclonal Antibodies 3D structures Tau protein 3D structures

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