View source for 8kcu


==Cryo-EM structure of human gamma-secretase in complex with MK-0752==
<StructureSection load='8kcu' size='340' side='right'caption='[[8kcu]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8kcu]] is a 4 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=8KCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8KCU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7&#8491;</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=8kcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8kcu OCA], [https://pdbe.org/8kcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8kcu RCSB], [https://www.ebi.ac.uk/pdbsum/8kcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8kcu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PSN1_HUMAN PSN1_HUMAN] Defects in PSEN1 are a cause of Alzheimer disease type 3 (AD3) [MIM:[https://omim.org/entry/607822 607822]. AD3 is a familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.<ref>PMID:12058025</ref> <ref>PMID:7596406</ref> <ref>PMID:8634711</ref> <ref>PMID:8634712</ref> <ref>PMID:7651536</ref> <ref>PMID:7550356</ref> <ref>PMID:8733303</ref> <ref>PMID:9225696</ref> <ref>PMID:9298817</ref> <ref>PMID:9172170</ref> <ref>PMID:9833068</ref> <ref>PMID:9384602</ref> <ref>PMID:9521423</ref> <ref>PMID:10200054</ref> <ref>PMID:9719376</ref> <ref>PMID:9507958</ref> <ref>PMID:9831473</ref> <ref>PMID:10441572</ref> <ref>PMID:10090481</ref> <ref>PMID:10447269</ref> <ref>PMID:10533070</ref> <ref>PMID:10025789</ref> <ref>PMID:10208579</ref> <ref>PMID:10439444</ref> <ref>PMID:10631141</ref> <ref>PMID:10644793</ref> <ref>PMID:11027672</ref> [:]<ref>PMID:11710891</ref> <ref>PMID:11920851</ref> <ref>PMID:12048239</ref> <ref>PMID:12484344</ref> <ref>PMID:12493737</ref>   Defects in PSEN1 are a cause of frontotemporal dementia (FTD) [MIM:[https://omim.org/entry/600274 600274].  Defects in PSEN1 are the cause of cardiomyopathy dilated type 1U (CMD1U) [MIM:[https://omim.org/entry/613694 613694]. It is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:17186461</ref>   Defects in PSEN1 are the cause of familial acne inversa type 3 (ACNINV3) [MIM:[https://omim.org/entry/613737 613737]. A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.<ref>PMID:20929727</ref> 
== Function ==
[https://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> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Guo X]]
[[Category: Kai U]]
[[Category: Lei J]]
[[Category: Li H]]
[[Category: Shi Y]]
[[Category: Yan C]]
[[Category: Zhou R]]