2o5y: Difference between revisions
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<StructureSection load='2o5y' size='340' side='right' caption='[[2o5y]], [[Resolution|resolution]] 2.85Å' scene=''> | <StructureSection load='2o5y' size='340' side='right' caption='[[2o5y]], [[Resolution|resolution]] 2.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2o5y]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2o5y]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O5Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2O5Y FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o5x|2o5x]], [[2o5z|2o5z]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o5x|2o5x]], [[2o5z|2o5z]]</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=2o5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o5y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2o5y RCSB], [http://www.ebi.ac.uk/pdbsum/2o5y PDBsum]</span></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=2o5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o5y OCA], [http://pdbe.org/2o5y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2o5y RCSB], [http://www.ebi.ac.uk/pdbsum/2o5y PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2o5y" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Lk3 transgenic mice]] | ||
[[Category: Verdino, P]] | [[Category: Verdino, P]] | ||
[[Category: Wilson, I A]] | [[Category: Wilson, I A]] | ||
Revision as of 17:11, 11 September 2015
Crystal structure of the 1E9 LeuH47Trp/ArgH100Trp Fab progesterone complexCrystal structure of the 1E9 LeuH47Trp/ArgH100Trp Fab progesterone complex
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMolecular recognition by the adaptive immune system relies on specific high-affinity antibody receptors that are generated from a restricted set of starting sequences through homologous recombination and somatic mutation. The steroid binding antibody DB3 and the catalytic Diels-Alderase antibody 1E9 derive from the same germ line sequences but exhibit very distinct specificities and functions. However, mutation of only two of the 36 sequence differences in the variable domains, Leu(H47)Trp and Arg(H100)Trp, converts 1E9 into a high-affinity steroid receptor with a ligand recognition profile similar to DB3. To understand how these changes switch binding specificity and function, we determined the crystal structures of the 1E9 Leu(H47)Trp/Arg(H100)Trp double mutant (1E9dm) as an unliganded Fab at 2.05 A resolution and in complex with two configurationally distinct steroids at 2.40 and 2.85 A. Surprisingly, despite the functional mimicry of DB3, 1E9dm employs a distinct steroid binding mechanism. Extensive structural rearrangements occur in the combining site, where residue H47 acts as a specificity switch and H100 adapts to different ligands. Unlike DB3, 1E9dm does not use alternative binding pockets or different sets of hydrogen-bonding interactions to bind configurationally distinct steroids. Rather, the different steroids are inserted more deeply into the 1E9dm combining site, creating more hydrophobic contacts that energetically compensate for the lack of hydrogen bonds. These findings demonstrate how subtle mutations within an existing molecular scaffold can dramatically modulate the function of immune receptors by inducing unanticipated, but compensating, mechanisms of ligand interaction. Closely related antibody receptors exploit fundamentally different strategies for steroid recognition.,Verdino P, Aldag C, Hilvert D, Wilson IA Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11725-30. Epub 2008 Aug 8. PMID:18689687[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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