3npz: Difference between revisions
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==Prolactin Receptor (PRLR) Complexed with the Natural Hormone (PRL)== | |||
<StructureSection load='3npz' size='340' side='right' caption='[[3npz]], [[Resolution|resolution]] 3.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3npz]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NPZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NPZ FirstGlance]. <br> | |||
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hCG_36753, PRL, RP3-404K8.1-001 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), Prlr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=3npz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3npz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3npz RCSB], [http://www.ebi.ac.uk/pdbsum/3npz PDBsum]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/np/3npz_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<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]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The most promising approach to targeting the tumor-growth-promoting actions of prolactin (PRL) mediated by its autocrine/paracrine pathway has been the development of specific PRL receptor (PRLR) antagonists. However, the optimization of such antagonists requires a thorough understanding of the activation mechanism of PRLR. We have thus conducted a systematic X-ray crystallographic study in order to visualize the successive steps of PRLR activation by PRL. We report here the structure at 3.35 A resolution of the 1:2 complex between natural PRL and two PRLR chains (PRLR1 and PRLR2), corresponding to the final activated state of PRLR. Further than our previously published structure involving an affinity-matured PRL variant, this structure allowed to visualize for the first time the loop L5 spanning PRLR2 residues Thr133-Phe140, revealing its central implication for the three intermolecular interfaces of the complex. We equally succeeded in obtaining a comprehensive picture of the PRLR-PRLR dimerization interface, also called stem-stem interface. Site-directed mutagenesis was conducted to probe the energetic importance of stem-stem contacts highlighted by the structure. Surprisingly, in spite of significant structural differences between the PRL/PRLR(2) complex and the growth hormone/growth hormone receptor 2 complex, our mutational data suggest that hot-spot residues that stabilize the receptor dimerization interface are equivalent in the two complexes. This study provides a new overall picture of the structural features of PRLR involved in stabilizing its complex with PRL. | |||
Structural Characterization of the Stem-Stem Dimerization Interface between Prolactin Receptor Chains Complexed with the Natural Hormone.,van Agthoven J, Zhang C, Tallet E, Raynal B, Hoos S, Baron B, England P, Goffin V, Broutin I J Mol Biol. 2010 Sep 25. PMID:20875426<ref>PMID:20875426</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Agthoven, J Van | [[Category: Agthoven, J Van]] | ||
[[Category: Broutin, I | [[Category: Broutin, I]] | ||
[[Category: England, P | [[Category: England, P]] | ||
[[Category: Goffin, V | [[Category: Goffin, V]] | ||
[[Category: Hormone]] | [[Category: Hormone]] | ||
[[Category: Hormone-hormone receptor complex]] | [[Category: Hormone-hormone receptor complex]] | ||
[[Category: Hormone-receptor complex]] | [[Category: Hormone-receptor complex]] | ||
[[Category: Protein protein complex]] | [[Category: Protein protein complex]] | ||
Revision as of 06:41, 19 December 2014
Prolactin Receptor (PRLR) Complexed with the Natural Hormone (PRL)
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