7zmk

Structure of human MFAP4 in complex with the Fab fragment of the AS0326 monoclonal antibody

spinqualitylabelsall models 7zmk, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zmk is a 24 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 3.4Å Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MFAP4_HUMAN Could be involved in calcium-dependent cell adhesion or intercellular interactions. May contribute to the elastic fiber assembly and/or maintenance (PubMed:26601954). Publication Abstract from PubMed Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin alpha(V)beta(3/5/6) ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Muller cells. Binding of the anti-MFAP4 antibody, hAS0326, makes MFAP4 inaccessible for integrin receptor interaction and thereby hAS0326 blocked endothelial cell motility in vitro. Intravitreal hAS0326 inhibited retinal vascular lesion area and neovessel volume in a laser-induced choroidal neovascularization mouse model, vascular permeability in streptozotocin-induced retinopathy and vascular leakage area in a chronic non-human primate model of DL-2-aminoadipic acid-induced retinopathy. One dose of hAS0326 showed duration of efficacy of at least 12 weeks in the latter model. Moreover, hAS0326-treatment significantly enriched gene ontology terms involving reduction of integrin binding. Our data suggest that hAS0326 constitutes a promising treatment of neovascularization and vascular leakage in retinal diseases. Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.,Schlosser A, Pilecki B, Allen C, Benest AV, Lynch AP, Hua J, Ved N, Blackley Z, Andersen TL, Hennig D, Graversen JH, Moller S, Skallerup S, Ormhoj M, Lange C, Agostini HT, Grauslund J, Heegaard S, Dacheva I, Koss M, Hu W, Iglesias B, Lawrence MS, Beck HC, Steffensen LB, Laursen NS, Andersen GR, Holmskov U, Bates DO, Sorensen GL Mol Ther. 2025 Jan 25:S1525-0016(25)00042-5. doi: 10.1016/j.ymthe.2025.01.038. PMID:39863929 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA