8g2o

Fab structure - Anti-ApoE-7C11 antibodyFab structure - Anti-ApoE-7C11 antibody

Structural highlights 8g2o is a 2 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 1.7Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed INTRODUCTION: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs). METHODS: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions. RESULTS: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD. APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.,Marino C, Perez-Corredor P, O'Hare M, Heuer A, Chmielewska N, Gordon H, Chandrahas AS, Gonzalez-Buendia L, Delgado-Tirado S, Doan TH, Vanderleest TE, Arevalo-Alquichire S, Obar RA, Ortiz-Cordero C, Villegas A, Sepulveda-Falla D, Kim LA, Lopera F, Mahley R, Huang Y, Quiroz YT, Arboleda-Velasquez JF Alzheimers Dement. 2024 Feb;20(2):819-836. doi: 10.1002/alz.13436. Epub 2023 Oct , 4. PMID:37791598 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 8g2o, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image