View source for 3npz


==Prolactin Receptor (PRLR) Complexed with the Natural Hormone (PRL)==
<StructureSection load='3npz' size='340' side='right'caption='[[3npz]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3npz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://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 [https://proteopedia.org/fgij/fg.htm?mol=3NPZ 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]] 3.35&#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=3npz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3npz OCA], [https://pdbe.org/3npz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3npz RCSB], [https://www.ebi.ac.uk/pdbsum/3npz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3npz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PRL_HUMAN PRL_HUMAN] Prolactin acts primarily on the mammary gland by promoting lactation.
== 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/initialview03.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/main_output.php?pdb_ID=3npz ConSurf].
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Prolactin|Prolactin]]
*[[Prolactin receptor|Prolactin receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Broutin I]]
[[Category: England P]]
[[Category: Goffin V]]
[[Category: Van Agthoven J]]