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| | <StructureSection load='2p3w' size='340' side='right'caption='[[2p3w]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='2p3w' size='340' side='right'caption='[[2p3w]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2p3w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P3W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P3W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2p3w]] is a 2 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=2P3W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P3W FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2joa|2joa]]</div></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]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HTRA3, PRSP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3w OCA], [https://pdbe.org/2p3w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p3w RCSB], [https://www.ebi.ac.uk/pdbsum/2p3w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p3w 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=2p3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3w OCA], [https://pdbe.org/2p3w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p3w RCSB], [https://www.ebi.ac.uk/pdbsum/2p3w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p3w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HTRA3_HUMAN HTRA3_HUMAN]] Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.<ref>PMID:21321049</ref>
| + | [https://www.uniprot.org/uniprot/HTRA3_HUMAN HTRA3_HUMAN] Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.<ref>PMID:21321049</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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Appleton, B A]] | + | [[Category: Appleton BA]] |
| - | [[Category: Wiesmann, C]] | + | [[Category: Wiesmann C]] |
| - | [[Category: Pdz domain]]
| + | |
| - | [[Category: Phage derived high affinity ligand]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
HTRA3_HUMAN Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.[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
High-temperature requirement A (HtrA) and its homologs contain a serine protease domain followed by one or two PDZ domains. Bacterial HtrA proteins and the mitochondrial protein HtrA2/Omi maintain cell function by acting as both molecular chaperones and proteases to manage misfolded proteins. The biological roles of the mammalian family members HtrA1 and HtrA3 are less clear. We report a detailed structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3 using peptide libraries and affinity assays to define specificity, structural studies to view the molecular details of ligand recognition, and alanine scanning mutagenesis to investigate the energetic contributions of individual residues to ligand binding. In common with HtrA2/Omi, we show that the PDZ domains of HtrA1 and HtrA3 recognize hydrophobic polypeptides, and while C-terminal sequences are preferred, internal sequences are also recognized. However, the details of the interactions differ, as different domains rely on interactions with different residues within the ligand to achieve high affinity binding. The results suggest that mammalian HtrA PDZ domains interact with a broad range of hydrophobic binding partners. This promiscuous specificity resembles that of bacterial HtrA family members and suggests a similar function for recognizing misfolded polypeptides with exposed hydrophobic sequences. Our results support a common activation mechanism for the HtrA family, whereby hydrophobic peptides bind to the PDZ domain and induce conformational changes that activate the protease. Such a mechanism is well suited to proteases evolved for the recognition and degradation of misfolded proteins.
Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3.,Runyon ST, Zhang Y, Appleton BA, Sazinsky SL, Wu P, Pan B, Wiesmann C, Skelton NJ, Sidhu SS Protein Sci. 2007 Nov;16(11):2454-71. PMID:17962403[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Singh H, Endo Y, Nie G. Decidual HtrA3 negatively regulates trophoblast invasion during human placentation. Hum Reprod. 2011 Apr;26(4):748-57. doi: 10.1093/humrep/der019. Epub 2011 Feb 14. PMID:21321049 doi:http://dx.doi.org/10.1093/humrep/der019
- ↑ Runyon ST, Zhang Y, Appleton BA, Sazinsky SL, Wu P, Pan B, Wiesmann C, Skelton NJ, Sidhu SS. Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3. Protein Sci. 2007 Nov;16(11):2454-71. PMID:17962403 doi:http://dx.doi.org/16/11/2454
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