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| | ==PC1/3 DCSG sorting domain structure in DPC== | | ==PC1/3 DCSG sorting domain structure in DPC== |
| - | <StructureSection load='2kdt' size='340' side='right'caption='[[2kdt]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kdt' size='340' side='right'caption='[[2kdt]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kdt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KDT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kdt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KDT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pcsk1, Att-1, Nec-1, Nec1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Proprotein_convertase_1 Proprotein convertase 1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.93 3.4.21.93] </span></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=2kdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdt OCA], [https://pdbe.org/2kdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kdt RCSB], [https://www.ebi.ac.uk/pdbsum/2kdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kdt 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=2kdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdt OCA], [https://pdbe.org/2kdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kdt RCSB], [https://www.ebi.ac.uk/pdbsum/2kdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kdt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NEC1_MOUSE NEC1_MOUSE]] Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin and insulin.
| + | [https://www.uniprot.org/uniprot/NEC1_MOUSE NEC1_MOUSE] Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin and insulin. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Proprotein convertase 1]] | + | [[Category: Di Lello P]] |
| - | [[Category: Dikeakos, J D]] | + | [[Category: Dikeakos JD]] |
| - | [[Category: Ghirlando, R]] | + | [[Category: Ghirlando R]] |
| - | [[Category: Lacombe, M J]] | + | [[Category: Lacombe MJ]] |
| - | [[Category: Legault, P]] | + | [[Category: Legault P]] |
| - | [[Category: Lello, P Di]]
| + | [[Category: Omichinski JG]] |
| - | [[Category: Omichinski, J G]] | + | [[Category: Reudelhuber TL]] |
| - | [[Category: Reudelhuber, T L]] | + | |
| - | [[Category: Calcium]]
| + | |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Cytoplasmic vesicle]]
| + | |
| - | [[Category: Glycoprotein]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Prohorme convertase]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Secretory granule]]
| + | |
| - | [[Category: Serine protease]]
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| - | [[Category: Zymogen]]
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| Structural highlights
Function
NEC1_MOUSE Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin and insulin.
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
Several peptide hormones are initially synthesized as inactive precursors. It is only on entry of these prohormones and their processing proteases into dense core secretory granules (DCSGs) that the precursors are cleaved to generate their active forms. Prohormone convertase (PC)1/3 is a processing protease that is targeted to DCSGs. The signal for targeting PC1/3 to DCSGs resides in its carboxy-terminal tail (PC1/3(617-753)), where 3 regions (PC1/3(617-625), PC1/3(665-682), and PC1/3(711-753)) are known to aid in sorting and membrane association. In this article, we have determined a high-resolution structure of the extreme carboxy-terminal sorting domain, PC1/3(711-753) in micelles by NMR spectroscopy. PC1/3(711-753) contains 2 alpha helices located between residues 722-728 and 738-750. Functional assays demonstrate that the second helix (PC1/3(738-750)) is necessary and sufficient to target a constitutively secreted protein to granules, and that L(745) anchors a hydrophobic patch that is critical for sorting. Also, we demonstrate that calcium binding by the second helix of PC1/3(711-753) promotes aggregation of the domain via the hydrophobic patch centered on L(745). These results provide a structure-function analysis of a DCSG-sorting domain, and reveal the importance of a hydrophobic patch and calcium binding in controlling the sorting of proteins containing alpha helices to DCSGs.
Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease.,Dikeakos JD, Di Lello P, Lacombe MJ, Ghirlando R, Legault P, Reudelhuber TL, Omichinski JG Proc Natl Acad Sci U S A. 2009 May 5;106(18):7408-13. Epub 2009 Apr 17. PMID:19376969[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dikeakos JD, Di Lello P, Lacombe MJ, Ghirlando R, Legault P, Reudelhuber TL, Omichinski JG. Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7408-13. Epub 2009 Apr 17. PMID:19376969
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