3mzg

From Proteopedia

(Difference between revisions)

Revision as of 12:34, 4 August 2016

Crystal structure of a human prolactin receptor antagonist in complex with the extracellular domain of the human prolactin receptor

Structural highlights

3mzg is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3n06, 3n0p, 3ncb, 3ncc, 3nce, 3ncf
Gene:	PRL, Prolactin (HUMAN), PRLR, Prolactin receptor (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PRL_HUMAN] Prolactin acts primarily on the mammary gland by promoting lactation. [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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human prolactin (hPRL), a member of the family of hematopoietic cytokines, functions as both an endocrine hormone and autocrine/paracrine growth factor. We have previously demonstrated that recognition of the hPRL receptor (hPRLr) depends strongly on solution acidity over the physiologic range from pH 6 &- 8. The hPRL-receptor binding interface contains four histidines, whose protonation is hypothesized to regulate pH-dependent receptor recognition. Here, we systematically dissect its molecular origin by characterizing the consequences of His to Ala mutations on pH-dependent receptor-binding kinetics, site-specific histidine protonation, and high resolution structures of the intermolecular interface. Thermodynamic modeling of the pH dependence to receptor-binding affinity reveals large changes in site-specific protonation constants for a majority of interface histidines upon complexation. Removal of individual His imidazoles reduces these perturbations in protonation constants, which is most likely explained by the introduction of solvent-filled, buried cavities in the crystallographic structures without inducing significant conformational rearrangements.

Two independent histidines, one in human prolactin and one in its receptor, are critical for pH dependent receptor recognition and activation.,Kulkarni MV, Tettamanzi MC, Murphy JW, Keeler C, Myszka DG, Chayen NE, Lolis EJ, Hodsdon ME J Biol Chem. 2010 Sep 30. PMID:20889499^[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
↑ Kulkarni MV, Tettamanzi MC, Murphy JW, Keeler C, Myszka DG, Chayen NE, Lolis EJ, Hodsdon ME. Two independent histidines, one in human prolactin and one in its receptor, are critical for pH dependent receptor recognition and activation. J Biol Chem. 2010 Sep 30. PMID:20889499 doi:10.1074/jbc.M110.172072

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3mzg"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a human prolactin receptor antagonist in complex with the extracellular domain of the human prolactin receptor==
 <StructureSection load='3mzg' size='340' side='right' caption='[[3mzg]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3mzg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MZG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3mzg]] 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=3MZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MZG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n06|3n06]], [[3n0p|3n0p]], [[3ncb|3ncb]], [[3ncc|3ncc]], [[3nce|3nce]], [[3ncf|3ncf]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRL, Prolactin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PRLR, Prolactin receptor ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRL, Prolactin ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRLR, Prolactin receptor ([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=3mzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mzg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mzg RCSB], [http://www.ebi.ac.uk/pdbsum/3mzg 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=3mzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mzg OCA], [http://pdbe.org/3mzg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mzg RCSB], [http://www.ebi.ac.uk/pdbsum/3mzg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mzg ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mzg ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3mzg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Prolactin|Prolactin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Chayen, N E]]
 [[Category: Hodsdon, M E]]

3mzg

From Proteopedia

Revision as of 12:34, 4 August 2016

Crystal structure of a human prolactin receptor antagonist in complex with the extracellular domain of the human prolactin receptor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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