View source for 4ri0


==Serine Protease HtrA3, mutationally inactivated==
<StructureSection load='4ri0' size='340' side='right'caption='[[4ri0]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ri0]] is a 3 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=4RI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RI0 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]] 3.272&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4ri0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ri0 OCA], [https://pdbe.org/4ri0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ri0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ri0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ri0 ProSAT]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human HtrA3 protease, which induces mitochondria-mediated apoptosis, can be a tumor suppressor and a potential therapeutic target in the treatment of cancer. However, there is little information about its structure and biochemical properties. HtrA3 is composed of an N-terminal domain not required for proteolytic activity, a central serine protease domain and a C-terminal PDZ domain. HtrA3S, its short natural isoform, lacks the PDZ domain which is substituted by a stretch of 7 C-terminal amino acid residues, unique for this isoform. This paper presents the crystal structure of the HtrA3 protease domain together with the PDZ domain (DeltaN-HtrA3), showing that the protein forms a trimer whose protease domains are similar to those of human HtrA1 and HtrA2. The DeltaN-HtrA3 PDZ domains are placed in a position intermediate between that in the flat saucer-like HtrA1 SAXS structure and the compact pyramidal HtrA2 X-ray structure. The PDZ domain interacts closely with the LB loop of the protease domain in a way not found in other human HtrAs. DeltaN-HtrA3 with the PDZ removed (DeltaN-HtrA3-DeltaPDZ) and an N-terminally truncated HtrA3S (DeltaN-HtrA3S) were fully active at a wide range of temperatures and their substrate affinity was not impaired. This indicates that the PDZ domain is dispensable for HtrA3 activity. As determined by size exclusion chromatography, DeltaN-HtrA3 formed stable trimers while both DeltaN-HtrA3-DeltaPDZ and DeltaN-HtrA3S were monomeric. This suggests that the presence of the PDZ domain, unlike in HtrA1 and HtrA2, influences HtrA3 trimer formation. The unique C-terminal sequence of DeltaN-HtrA3S appeared to have little effect on activity and oligomerization. Additionally, we examined the cleavage specificity of DeltaN-HtrA3. Results reported in this paper provide new insights into the structure and function of DeltaN-HtrA3, which seems to have a unique combination of features among human HtrA proteases.

Structural and Functional Analysis of Human HtrA3 Protease and Its Subdomains.,Glaza P, Osipiuk J, Wenta T, Zurawa-Janicka D, Jarzab M, Lesner A, Banecki B, Skorko-Glonek J, Joachimiak A, Lipinska B PLoS One. 2015 Jun 25;10(6):e0131142. doi: 10.1371/journal.pone.0131142., eCollection 2015. PMID:26110759<ref>PMID:26110759</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4ri0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Glaza P]]
[[Category: Joachimiak A]]
[[Category: Lipinska B]]
[[Category: Osipiuk J]]
[[Category: Wenta T]]