View source for 6my4


==Crystal structure of the dimeric bH1-Fab variant [HC-Y33W,HC-D98M,HC-G99M,LC-S30bR]==
<StructureSection load='6my4' size='340' side='right'caption='[[6my4]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6my4]] 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=6MY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MY4 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]] 1.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6my4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6my4 OCA], [https://pdbe.org/6my4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6my4 RCSB], [https://www.ebi.ac.uk/pdbsum/6my4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6my4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/V9HW68_HUMAN V9HW68_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Solution stability is an important factor in the optimization of engineered biotherapeutic candidates such as monoclonal antibodies because of its possible effects on manufacturability, pharmacology, efficacy and safety. A detailed atomic understanding of the mechanisms governing self-association of natively folded protein monomers is required to devise predictive tools to guide screening and re-engineering along the drug development pipeline. We investigated pairs of affinity-matured full-size antibodies and observed drastically different propensities to aggregate from variants differing by a single amino-acid. Biophysical testing showed that antigen-binding fragments (Fabs) from the aggregating antibodies also reversibly associated with equilibrium dissociation constants in the low-micromolar range. Crystal structures (PDB accession codes 6MXR, 6MXS, 6MY4, 6MY5) and bottom-up hydrogen-exchange mass spectrometry revealed that Fab self-association occurs in a symmetric mode that involves the antigen complementarity-determining regions. Subtle local conformational changes incurred upon point mutation of monomeric variants foster formation of complementary polar interactions and hydrophobic contacts to generate a dimeric Fab interface. Testing of popular in silico tools generally indicated low reliabilities for predicting the aggregation propensities observed. A structure-aggregation data set is provided here in order to stimulate further improvements of in silico tools for prediction of native aggregation. Incorporation of intermolecular docking, conformational flexibility, and short-range packing interactions may all be necessary features of the ideal algorithm.

Binding symmetry and surface flexibility mediate antibody self-association.,Schrag JD, Picard ME, Gaudreault F, Gagnon LP, Baardsnes J, Manenda MS, Sheff J, Deprez C, Baptista C, Hogues H, Kelly JF, Purisima EO, Shi R, Sulea T MAbs. 2019 Jul 18:1-19. doi: 10.1080/19420862.2019.1632114. PMID:31318308<ref>PMID:31318308</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6my4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Manenda M]]
[[Category: Picard M-E]]
[[Category: Shi R]]