View source for 4z95


==Fab structure of antibody S1-15 in complex with ssDNA DNA, 5'-5(dT)-p-3'==
<StructureSection load='4z95' size='340' side='right'caption='[[4z95]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4z95]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z95 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4z95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z95 OCA], [https://pdbe.org/4z95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z95 RCSB], [https://www.ebi.ac.uk/pdbsum/4z95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z95 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Septic shock is a leading cause of death, and, results from an inflammatory cascade triggered by the presence of microbial products in the blood. Certain LPS from Gram-negative bacteria are very potent inducers and responsible for a high percentage of septic shock cases. Despite decades of research, mAbs specific for lipid A (the endotoxic principle of LPS) have not been successfully developed into a clinical treatment for sepsis. To understand the molecular basis for the observed inability to translate in vitro specificity for lipid A into clinical potential, the structures of antigen binding fragments of mAbs S1-15 and A6 have been determined unliganded and in complex with lipid A carbohydrate backbone. The two antibodies have separate germ-line origins that generate two markedly different combining-site pockets that are complementary both in shape and charge to the antigen. MAb A6 binds lipid A through both variable light and heavy chain residues, while S1-15 utilizes exclusively the variable heavy chain. Both antibodies bind lipid A such that the GlcN-O6 attachment point for the core oligosaccharide is buried in the combining site, which explains the lack of LPS recognition. Longstanding reports of polyspecificity of anti-lipid A antibodies towards single stranded DNA combined with observed homology of S1-15 and A6 and the reports of several single stranded DNA-specific mAbs prompted the determination of the structure of S1-15 in complex with ssDNA fragments, which may provide clues into the genesis of autoimmune diseases such as systemic lupus erythematosus, thyroiditis, and rheumatic autoimmune diseases.

Structural Basis for Antibody Recognition of Lipid A: Insights to Polyspecificity Toward Single Stranded DNA.,Haji-Ghassemi O, Muller-Loennies S, Rodriguez T, Brade L, Kosma P, Brade H, Evans SV J Biol Chem. 2015 Jun 17. pii: jbc.M115.657874. PMID:26085093<ref>PMID:26085093</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4z95" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Evans SV]]
[[Category: Haji-Ghassemi O]]