4eow | pdb_00004eow

Crystal structure of a disease-associated anti-human GM-CSF autoantibody MB007

spinqualitylabelsall models 4eow, resolution 1.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4eow is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Polyclonal autoantibodies against human granulocyte macrophage- colony stimulating factor (hGM-CSF) are a hallmark of pulmonary alveolar proteinosis (PAP) affection and several other reported autoimmune diseases. MB007 is a high affinity anti-human GM-CSF autoantibody isolated from a patient suffering from PAP which shows only modest neutralization of GM-CSF bioactivity. We describe the first crystal structure of a cytokine directed human IgG1lambda autoantibody binding fragment (Fab) at 1.9 A resolution. Its CDR3-H substantially differs from all previously reported VH7 germline IgG1 structures. We derive a reliable model of the antigen:autoantibody complex by using NMR chemical shift perturbation data in combination with computational methods. Superposition of the modeled complex structure with the human GM-CSF/GM-CSF ternary receptor complex reveals only little overlap between receptor and Fab when bound to GM-CSF. Our model provides a structural basis for understanding the mode-of-action of the MB007 autoantibody. Molecular structure of human GM-CSF in complex with a disease-associated anti-human GM-CSF autoantibody and its potential biological implications.,Blech M, Seeliger D, Kistler B, Bauer MM, Hafner M, Horer S, Zeeb M, Nar H, Park JE Biochem J. 2012 Jul 27. PMID:22839360 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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