6idf: Difference between revisions
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<StructureSection load='6idf' size='340' side='right' caption='[[6idf]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='6idf' size='340' side='right' caption='[[6idf]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6idf]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IDF FirstGlance]. <br> | <table><tr><td colspan='2'>[[6idf]] is a 5 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=6IDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IDF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCSTN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APH1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PEN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6idf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6idf OCA], [http://pdbe.org/6idf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6idf RCSB], [http://www.ebi.ac.uk/pdbsum/6idf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6idf ProSAT]</span></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=6idf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6idf OCA], [http://pdbe.org/6idf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6idf RCSB], [http://www.ebi.ac.uk/pdbsum/6idf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6idf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PEN2_HUMAN PEN2_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.<ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. [[http://www.uniprot.org/uniprot/APH1A_HUMAN APH1A_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.<ref>PMID:12297508</ref> <ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN]] Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis.<ref>PMID:10545183</ref> <ref>PMID:10593990</ref> <ref>PMID:10206644</ref> <ref>PMID:10899933</ref> <ref>PMID:10811883</ref> <ref>PMID:11226248</ref> <ref>PMID:15341515</ref> <ref>PMID:16305624</ref> | [[http://www.uniprot.org/uniprot/PEN2_HUMAN PEN2_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.<ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. [[http://www.uniprot.org/uniprot/APH1A_HUMAN APH1A_HUMAN]] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.<ref>PMID:12297508</ref> <ref>PMID:12522139</ref> <ref>PMID:12763021</ref> [[http://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN]] Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis.<ref>PMID:10545183</ref> <ref>PMID:10593990</ref> <ref>PMID:10206644</ref> <ref>PMID:10899933</ref> <ref>PMID:10811883</ref> <ref>PMID:11226248</ref> <ref>PMID:15341515</ref> <ref>PMID:16305624</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aberrant cleavage of Notch by gamma-secretase leads to several types of cancer, but how gamma-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human gamma-secretase in complex with a Notch fragment at a resolution of 2.7 A. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal beta-strand of the Notch fragment forms a beta-sheet with two substrate-induced beta-strands of PS1 on the intracellular side. Formation of the hybrid beta-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by gamma-secretase. | |||
Structural basis of Notch recognition by human gamma-secretase.,Yang G, Zhou R, Zhou Q, Guo X, Yan C, Ke M, Lei J, Shi Y Nature. 2019 Jan;565(7738):192-197. doi: 10.1038/s41586-018-0813-8. Epub 2018 Dec, 31. PMID:30598546<ref>PMID:30598546</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6idf" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Guo, X]] | [[Category: Guo, X]] | ||
[[Category: Ke, M]] | [[Category: Ke, M]] | ||