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| | ==Crystal Structure of Human Placental Lactogen== | | ==Crystal Structure of Human Placental Lactogen== |
| - | <StructureSection load='1z7c' size='340' side='right' caption='[[1z7c]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='1z7c' size='340' side='right'caption='[[1z7c]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1z7c]] is a 1 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=1Z7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z7C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1z7c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z7C FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2Å</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=1z7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z7c OCA], [http://pdbe.org/1z7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z7c RCSB], [http://www.ebi.ac.uk/pdbsum/1z7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1z7c 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=1z7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z7c OCA], [https://pdbe.org/1z7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z7c RCSB], [https://www.ebi.ac.uk/pdbsum/1z7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z7c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CSH_HUMAN CSH_HUMAN]] Produced only during pregnancy and is involved in stimulating lactation, fetal growth and metabolism. Does not interact with GHR but only activates PRLR through zinc-induced dimerization.<ref>PMID:16546209</ref> | + | [https://www.uniprot.org/uniprot/CSH1_HUMAN CSH1_HUMAN] Produced only during pregnancy and is involved in stimulating lactation, fetal growth and metabolism. Does not interact with GHR but only activates PRLR through zinc-induced dimerization.<ref>PMID:16546209</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kossiakoff, A A]] | + | [[Category: Large Structures]] |
| - | [[Category: Walsh, S T.R]] | + | [[Category: Kossiakoff AA]] |
| - | [[Category: Four-helix bundle protein]] | + | [[Category: Walsh STR]] |
| - | [[Category: Hormone-growth factor complex]]
| + | |
| Structural highlights
Function
CSH1_HUMAN Produced only during pregnancy and is involved in stimulating lactation, fetal growth and metabolism. Does not interact with GHR but only activates PRLR through zinc-induced dimerization.[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
In primates, placental lactogen (PL) is a pituitary hormone with fundamental roles during pregnancy involving fetal growth, metabolism, and stimulating lactation in the mother. Human placental lactogen (hPL) is highly conserved with human growth hormone (hGH) and both hormones bind to the hPRLR extracellular domain (ECD), the first step in receptor homodimerization, in a Zn2+-dependent manner. A modified surface plasmon resonance method was developed to measure the kinetics for hPL and hGH binding to the hPRLR ECD, with and without Zn2+ and showed that hPL has about a tenfold higher affinity for the hPRLR ECD1 than hGH. The crystal structure of the free state of hPL has been determined to 2.0 A resolution showing the molecule possesses an overall structure similar to other long chain four-helix bundle cytokines. Comparison of the free hPL structure with the 1:1 complex structure of hGH bound to the hPRLR ECD1 suggests that two surface loops undergo conformational changes >10 A upon binding. An 18 residue Ala-scan was used to characterize the binding energy epitope for the site 1 interface of hPL. Individual alanine substitutions at five positions reduced binding affinity by a DeltaDeltaG > or = 3 kcal mol(-1). A comparison of the hPL site 1 epitope with that previously determined for hGH indicates contributions of individual residues track reasonably well between hPL and hGH. In particular, residues involved in the zinc-binding site and Lys172 constitute the principal binding determinants for both hormones. However, several residues that are identical between hPL and hGH contribute quite differently to the binding of the hPRLR ECD1. Additionally, the overall magnitudes of the DeltaDeltaG changes observed from the Ala-scan of hPL were markedly larger than those determined in the comparative scan of hGH to the hPRLR ECD1. The structural and biophysical data presented here show that subtle changes in the structural context of an interaction can lead to significantly different effects at the individual residue level.
Crystal structure and site 1 binding energetics of human placental lactogen.,Walsh ST, Kossiakoff AA J Mol Biol. 2006 May 5;358(3):773-84. Epub 2006 Mar 2. PMID:16546209[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Walsh ST, Kossiakoff AA. Crystal structure and site 1 binding energetics of human placental lactogen. J Mol Biol. 2006 May 5;358(3):773-84. Epub 2006 Mar 2. PMID:16546209 doi:10.1016/j.jmb.2006.02.038
- ↑ Walsh ST, Kossiakoff AA. Crystal structure and site 1 binding energetics of human placental lactogen. J Mol Biol. 2006 May 5;358(3):773-84. Epub 2006 Mar 2. PMID:16546209 doi:10.1016/j.jmb.2006.02.038
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