4k3h: Difference between revisions
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==Immunoglobulin lambda variable domain L5(L89S) fluorogen activationg protein in complex with malachite green== | ==Immunoglobulin lambda variable domain L5(L89S) fluorogen activationg protein in complex with malachite green== | ||
<StructureSection load='4k3h' size='340' side='right' caption='[[4k3h]], [[Resolution|resolution]] 2.45Å' scene=''> | <StructureSection load='4k3h' size='340' side='right' caption='[[4k3h]], [[Resolution|resolution]] 2.45Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1OM:4-{BIS[4-(DIMETHYLAMINO)PHENYL]METHYL}PHENOL'>1OM</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1OM:4-{BIS[4-(DIMETHYLAMINO)PHENYL]METHYL}PHENOL'>1OM</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k3g|4k3g]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k3g|4k3g]]</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=4k3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k3h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k3h RCSB], [http://www.ebi.ac.uk/pdbsum/4k3h 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=4k3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k3h OCA], [http://pdbe.org/4k3h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k3h RCSB], [http://www.ebi.ac.uk/pdbsum/4k3h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k3h ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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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 4k3h" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 19:55, 5 August 2016
Immunoglobulin lambda variable domain L5(L89S) fluorogen activationg protein in complex with malachite greenImmunoglobulin lambda variable domain L5(L89S) fluorogen activationg protein in complex with malachite green
Structural highlights
Publication Abstract from PubMedWe report that a symmetric small-molecule ligand mediates the assembly of antibody light chain variable domains (VLs) into a correspondent symmetric ternary complex with novel interfaces. The L5* fluorogen activating protein is a VL domain that binds malachite green (MG) dye to activate intense fluorescence. Crystallography of liganded L5* reveals a 2:1 protein:ligand complex with inclusive C2 symmetry, where MG is almost entirely encapsulated between an antiparallel arrangement of the two VL domains. Unliganded L5* VL domains crystallize as a similar antiparallel VL/VL homodimer. The complementarity-determining regions are spatially oriented to form novel VL/VL and VL/ligand interfaces that tightly constrain a propeller conformer of MG. Binding equilibrium analysis suggests highly cooperative assembly to form a very stable VL/MG/VL complex, such that MG behaves as a strong chemical inducer of dimerization. Fusion of two VL domains into a single protein tightens MG binding over 1000-fold to low picomolar affinity without altering the large binding enthalpy, suggesting that bonding interactions with ligand and restriction of domain movements make independent contributions to binding. Fluorescence activation of a symmetrical fluorogen provides a selection mechanism for the isolation and directed evolution of ternary complexes where unnatural symmetric binding interfaces are favored over canonical antibody interfaces. As exemplified by L5*, these self-reporting complexes may be useful as modulators of protein association or as high-affinity protein tags and capture reagents. Malachite Green Mediates Homodimerization of Antibody V Domains to Form a Fluorescent Ternary Complex with Singular Symmetric Interfaces.,Szent-Gyorgyi C, Stanfield RL, Andreko S, Dempsey A, Ahmed M, Capek S, Waggoner AS, Wilson IA, Bruchez MP J Mol Biol. 2013 Aug 23. pii: S0022-2836(13)00534-2. doi:, 10.1016/j.jmb.2013.08.014. PMID:23978698[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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