6y6c

TREM2 extracellular domain (19-174) in complex with single-chain variable fragment (scFv-4)

spinqualitylabelsall models 6y6c, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6y6c is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mutations in TREM2, a receptor expressed by microglia in the brain, are associated with an increased risk of neurodegeneration, including Alzheimer's disease. Numerous studies support a role for TREM2 in sensing damaging stimuli and triggering signaling cascades necessary for neuroprotection. Despite its significant role, ligands and regulators of TREM2 activation, and the mechanisms governing TREM2-dependent responses and its cleavage from the membrane, remain poorly characterized. Here, we present phage display generated antibody single-chain variable fragments (scFvs) to human TREM2 immunoglobulin-like domain. Co-crystal structures revealed the binding of two scFvs to an epitope on the TREM2 domain distal to the putative ligand-binding site. Enhanced functional activity was observed for oligomeric scFv species, which inhibited the production of soluble TREM2 in a HEK293 cell model. We hope that detailed characterization of their epitopes and properties will facilitate the use of these renewable binders as structural and functional biology tools for TREM2 research. Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain.,Szykowska A, Chen Y, Smith TB, Preger C, Yang J, Qian D, Mukhopadhyay SM, Wigren E, Neame SJ, Graslund S, Persson H, Atkinson PJ, Di Daniel E, Mead E, Wang J, Davis JB, Burgess-Brown NA, Bullock AN Structure. 2021 Nov 4;29(11):1241-1252.e5. doi: 10.1016/j.str.2021.06.010. Epub , 2021 Jul 6. PMID:34233201 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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