1lcy

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[[Image:1lcy.gif|left|200px]]<br /><applet load="1lcy" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1lcy, resolution 2.00&Aring;" />
 
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'''Crystal Structure of the Mitochondrial Serine Protease HtrA2'''<br />
 
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==Overview==
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==Crystal Structure of the Mitochondrial Serine Protease HtrA2==
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HtrA2/Omi, a mitochondrial serine protease in mammals, is important in programmed cell death. However, the underlining mechanism of HtrA2/Omi-mediated apoptosis remains unclear. Analogous to the bacterial homolog HtrA (DegP), the mature HtrA2 protein contains a central serine protease domain and a C-terminal PDZ domain. The 2.0 A crystal structure of HtrA2/Omi reveals the formation of a pyramid-shaped homotrimer mediated exclusively by the serine protease domains. The peptide-binding pocket of the PDZ domain is buried in the intimate interface between the PDZ and the protease domains. Mutational analysis reveals that the monomeric HtrA2/Omi mutants are unable to induce cell death and are deficient in protease activity. The PDZ domain modulates HtrA2/Omi-mediated cell death activity by regulating its serine protease activity. These structural and biochemical observations provide an important framework for deciphering the mechanisms of HtrA2/Omi-mediated apoptosis.
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<StructureSection load='1lcy' size='340' side='right'caption='[[1lcy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1lcy]] 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=1LCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LCY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</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=1lcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lcy OCA], [https://pdbe.org/1lcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lcy RCSB], [https://www.ebi.ac.uk/pdbsum/1lcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lcy ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN] Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:[https://omim.org/entry/610297 610297]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:15961413</ref> <ref>PMID:18401856</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/HTRA2_HUMAN HTRA2_HUMAN] Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.<ref>PMID:15200957</ref> <ref>PMID:19502560</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lc/1lcy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1lcy ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Parkinson disease 13 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606441 606441]]
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*[[Proteinase 3D structures|Proteinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1LCY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LCY OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi., Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y, Nat Struct Biol. 2002 Jun;9(6):436-41. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11967569 11967569]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Alnemri, E S.]]
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[[Category: Alnemri ES]]
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[[Category: Chai, J.]]
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[[Category: Chai J]]
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[[Category: Li, P.]]
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[[Category: Li P]]
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[[Category: Li, W.]]
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[[Category: Li W]]
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[[Category: Shi, Y.]]
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[[Category: Shi Y]]
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[[Category: Srinivasula, S M.]]
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[[Category: Srinivasula SM]]
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[[Category: Wu, J W.]]
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[[Category: Wu JW]]
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[[Category: Zhang, Z.]]
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[[Category: Zhang Z]]
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[[Category: apoptosis]]
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[[Category: caspase activation]]
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[[Category: iap-binding]]
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[[Category: pdz domain]]
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[[Category: serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:43:55 2008''
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Current revision

Crystal Structure of the Mitochondrial Serine Protease HtrA2

PDB ID 1lcy

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