4i18

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human prolactin receptor complexed with Fab fragment

Structural highlights

4i18 is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.238Å
Ligands:	, ,
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=''>
+<StructureSection load='4i18' size='340' side='right'caption='[[4i18]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4i18]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I18 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I18 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4i18]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I18 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.238&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i18 OCA], [https://pdbe.org/4i18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i18 RCSB], [https://www.ebi.ac.uk/pdbsum/4i18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i18 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PRLR_HUMAN 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.<ref>PMID:12580759</ref>
+[https://www.uniprot.org/uniprot/PRLR_HUMAN 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.<ref>PMID:12580759</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[3D structures of antibody|3D structures of antibody]]
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Prolactin receptor|Prolactin receptor]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Large Structures]]
-[[Category: Duguid, E M]]
+[[Category: Mus musculus]]
-[[Category: Kouadio, J L]]
+[[Category: Duguid EM]]
-[[Category: Mukherjee, S]]
+[[Category: Kouadio JL]]
-[[Category: Cytokine]]
+[[Category: Mukherjee S]]
-[[Category: Immunoglobulin fold]]
-[[Category: Prolactin binding]]
-[[Category: Receptor signaling]]
-[[Category: Signaling protein]]

4i18

From Proteopedia

Current revision

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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