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==Crystal structure of the apo domain-swapped dimer Q108K:K40L:T51W mutant of human cellular retinol binding protein II==
<StructureSection load='6e51' size='340' side='right'caption='[[6e51]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6e51]] is a 1 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=6E51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E51 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]] 2.256&#8491;</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=6e51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e51 OCA], [https://pdbe.org/6e51 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e51 RCSB], [https://www.ebi.ac.uk/pdbsum/6e51 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e51 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6e51" style="background-color:#fffaf0;"></div>

==See Also==
*[[Retinol-binding protein 3D structures|Retinol-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Geiger J]]
[[Category: Ghanbarpour A]]