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4i18

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Revision as of 20:07, 11 August 2016

Crystal structure of human prolactin receptor complexed with Fab fragment

Structural highlights

4i18 is a 6 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	PRLR (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PRLR_HUMAN] This is a receptor for the anterior pituitary hormone prolactin (PRL). Isoform 4 is unable to transduce prolactin signaling. Isoform 6 is unable to transduce prolactin signaling.^[1]

Publication Abstract from PubMed

BackgroundMany receptors function by binding to multiple ligands, each eliciting a distinct biological output. The extracellular domain of the human prolactin receptor (hPRL-R) uses an identical epitope to bind to both prolactin (hPRL) and growth hormone (hGH), yet little is known about how each hormone binding event triggers the appropriate response.FindingsHere, we utilized a phage display library to generate synthetic antibodies (sABs) that preferentially modulate hPRL-R function in a hormone-dependent fashion. We determined the crystal structure of a sAB-hPRL-R complex, which revealed a novel allosteric mechanism of antagonism, whereby the sAB traps the receptor in a conformation more suitable for hGH binding than hPRL. This was validated by examining the effect of the sABs on hormone internalization via the hPRL-R and its downstream signaling pathway.ConclusionsThe findings suggest that subtle structural changes in the extracellular domain of hPRL-R induced by each hormone determine the biological output triggered by hormone binding. We conclude that sABs generated by phage display selection can detect these subtle structural differences, and therefore can be used to dissect the structural basis of receptor-ligand specificity.

Engineering synthetic antibody binders for allosteric inhibition of prolactin receptor signaling.,Rizk SS, Kouadio JL, Szymborska A, Duguid EM, Mukherjee S, Zheng J, Clevenger CV, Kossiakoff AA Cell Commun Signal. 2015 Jan 15;13(1):1. PMID:25589173^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Trott JF, Hovey RC, Koduri S, Vonderhaar BK. Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. J Mol Endocrinol. 2003 Feb;30(1):31-47. PMID:12580759
↑ Rizk SS, Kouadio JL, Szymborska A, Duguid EM, Mukherjee S, Zheng J, Clevenger CV, Kossiakoff AA. Engineering synthetic antibody binders for allosteric inhibition of prolactin receptor signaling. Cell Commun Signal. 2015 Jan 15;13(1):1. PMID:25589173 doi:http://dx.doi.org/10.1186/s12964-014-0080-8

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4i18"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human prolactin receptor complexed with Fab fragment==
 <StructureSection load='4i18' size='340' side='right' caption='[[4i18]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRLR ([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=4i18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i18 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i18 RCSB], [http://www.ebi.ac.uk/pdbsum/4i18 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=4i18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i18 OCA], [http://pdbe.org/4i18 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i18 RCSB], [http://www.ebi.ac.uk/pdbsum/4i18 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i18 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4i18" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Antibody|Antibody]]
+*[[Prolactin|Prolactin]]
+*[[3D structures of antibody|3D structures of antibody]]
 == References ==
 <references/>

4i18

From Proteopedia

Revision as of 20:07, 11 August 2016

Crystal structure of human prolactin receptor complexed with Fab fragment

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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