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| | <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=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k3h]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K3H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K3H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k3h]] is a 8 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=4K3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K3H FirstGlance]. <br> |
| - | </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" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4k3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k3h OCA], [https://pdbe.org/4k3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k3h RCSB], [https://www.ebi.ac.uk/pdbsum/4k3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k3h ProSAT]</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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stanfield, R L]] | + | [[Category: Stanfield RL]] |
| - | [[Category: Szent-Gyorgyi, C]] | + | [[Category: Szent-Gyorgyi C]] |
| - | [[Category: Wilson, I A]] | + | [[Category: Wilson IA]] |
| - | [[Category: Fluorescensce]]
| + | |
| - | [[Category: Immune system-inhibitor complex]]
| + | |
| - | [[Category: Immunoglobulin fold]]
| + | |
| - | [[Category: Malachite green]]
| + | |
| - | [[Category: O-mannosylation]]
| + | |
| - | [[Category: Thr27]]
| + | |
| Structural highlights
Publication Abstract from PubMed
We 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
- ↑ Szent-Gyorgyi C, Stanfield RL, Andreko S, Dempsey A, Ahmed M, Capek S, Waggoner AS, Wilson IA, Bruchez MP. Malachite Green Mediates Homodimerization of Antibody V Domains to Form a Fluorescent Ternary Complex with Singular Symmetric Interfaces. J Mol Biol. 2013 Aug 23. pii: S0022-2836(13)00534-2. doi:, 10.1016/j.jmb.2013.08.014. PMID:23978698 doi:http://dx.doi.org/10.1016/j.jmb.2013.08.014
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