View source for 4yhy


==Crystal structure of 309M3-B in complex with trimethylated Lys==
<StructureSection load='4yhy' size='340' side='right'caption='[[4yhy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yhy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YHY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YHY 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</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=4yhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yhy OCA], [https://pdbe.org/4yhy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yhy RCSB], [https://www.ebi.ac.uk/pdbsum/4yhy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yhy ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This "antigen clasping" produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody-antigen recognition and suggests a strategy for developing extremely specific antibodies.

Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation.,Hattori T, Lai D, Dementieva IS, Montano SP, Kurosawa K, Zheng Y, Akin LR, Swist-Rosowska KM, Grzybowski AT, Koide A, Krajewski K, Strahl BD, Kelleher NL, Ruthenburg AJ, Koide S Proc Natl Acad Sci U S A. 2016 Feb 9. pii: 201522691. PMID:26862167<ref>PMID:26862167</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yhy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dementieva IS]]
[[Category: Hattori T]]
[[Category: Koide S]]
[[Category: Montano SP]]