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==Crystal structure of a disease-associated anti-human GM-CSF autoantibody MB007== | |||
<StructureSection load='4eow' size='340' side='right' caption='[[4eow]], [[Resolution|resolution]] 1.97Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4eow]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EOW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EOW FirstGlance]. <br> | |||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eow OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eow RCSB], [http://www.ebi.ac.uk/pdbsum/4eow PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:22839360</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Blech, M | [[Category: Blech, M]] | ||
[[Category: Alpha-helical stretch in cdr3-h]] | [[Category: Alpha-helical stretch in cdr3-h]] | ||
[[Category: Autoantibody causing pap]] | [[Category: Autoantibody causing pap]] | ||