6e5r: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6e5r' size='340' side='right'caption='[[6e5r]], [[Resolution|resolution]] 2.59Å' scene=''> | <StructureSection load='6e5r' size='340' side='right'caption='[[6e5r]], [[Resolution|resolution]] 2.59Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6e5r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5R FirstGlance]. <br> | <table><tr><td colspan='2'>[[6e5r]] is a 2 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=6E5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5R FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RBP2, CRBP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6e5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5r OCA], [http://pdbe.org/6e5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e5r RCSB], [http://www.ebi.ac.uk/pdbsum/6e5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5r 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=6e5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5r OCA], [http://pdbe.org/6e5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e5r RCSB], [http://www.ebi.ac.uk/pdbsum/6e5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/RET2_HUMAN RET2_HUMAN]] Intracellular transport of retinol. | [[http://www.uniprot.org/uniprot/RET2_HUMAN RET2_HUMAN]] Intracellular transport of retinol. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein conformational switches or allosteric proteins play a key role in the regulation of many essential biological pathways. Nonetheless, the implementation of protein conformational switches in protein design applications has proven challenging, with only a few known examples that are not derivatives of naturally occurring allosteric systems. We have discovered that the domain swapped (DS) dimer of hCRBPII undergoes a large and robust conformational change upon retinal binding, making it a potentially powerful template for the design of protein conformational switches. Atomic resolution structures of the apo- and holo- forms illuminate a simple, mechanical mechanism involving sterically driven torsion angle flipping of two residues that drive the motion. We further demonstrate that the con-formational "readout" can be altered by addition of cross-domain disulfide bonds, also visualized at atomic resolution. Finally, as a proof of principle, we have created an allosteric metal binding site in the DS dimer, where ligand binding results in a reversible five-fold loss of metal binding affinity. The high resolution structure of the metal-bound variant illustrates a well-formed metal binding site at the inter-face of the two domains of the DS dimer, and confirms the design strategy for allosteric regulation. | |||
Engineering the hCRBPII domain-swapped dimer into a new class of protein switches.,Ghanbarpour A, Pinger C, Esmatpour Salmani R, Assar Z, Santos EM, Nosrati M, Pawlowski K, Spence D, Vasileiou C, Jin X, Borhan B, Geiger JH J Am Chem Soc. 2019 Sep 26. doi: 10.1021/jacs.9b04664. PMID:31557439<ref>PMID:31557439</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6e5r" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Geiger, J]] | [[Category: Geiger, J]] | ||
Revision as of 10:05, 16 October 2019
Crystal structure of the apo domain-swapped dimer Q108K:T51D:A28C mutant of human Cellular Retinol Binding Protein IICrystal structure of the apo domain-swapped dimer Q108K:T51D:A28C mutant of human Cellular Retinol Binding Protein II
Structural highlights
Function[RET2_HUMAN] Intracellular transport of retinol. Publication Abstract from PubMedProtein conformational switches or allosteric proteins play a key role in the regulation of many essential biological pathways. Nonetheless, the implementation of protein conformational switches in protein design applications has proven challenging, with only a few known examples that are not derivatives of naturally occurring allosteric systems. We have discovered that the domain swapped (DS) dimer of hCRBPII undergoes a large and robust conformational change upon retinal binding, making it a potentially powerful template for the design of protein conformational switches. Atomic resolution structures of the apo- and holo- forms illuminate a simple, mechanical mechanism involving sterically driven torsion angle flipping of two residues that drive the motion. We further demonstrate that the con-formational "readout" can be altered by addition of cross-domain disulfide bonds, also visualized at atomic resolution. Finally, as a proof of principle, we have created an allosteric metal binding site in the DS dimer, where ligand binding results in a reversible five-fold loss of metal binding affinity. The high resolution structure of the metal-bound variant illustrates a well-formed metal binding site at the inter-face of the two domains of the DS dimer, and confirms the design strategy for allosteric regulation. Engineering the hCRBPII domain-swapped dimer into a new class of protein switches.,Ghanbarpour A, Pinger C, Esmatpour Salmani R, Assar Z, Santos EM, Nosrati M, Pawlowski K, Spence D, Vasileiou C, Jin X, Borhan B, Geiger JH J Am Chem Soc. 2019 Sep 26. doi: 10.1021/jacs.9b04664. PMID:31557439[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||