5a63: Difference between revisions

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-'''Unreleased structure'''
-The entry 5a63 is ON HOLD
+==Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution.==
+<SX load='5a63' size='340' side='right' viewer='molstar' caption='[[5a63]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5a63]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4upc 4upc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A63 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5a63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a63 OCA], [https://pdbe.org/5a63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a63 RCSB], [https://www.ebi.ac.uk/pdbsum/5a63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a63 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Dysfunction of the intramembrane protease gamma-secretase is thought to cause Alzheimer's disease, with most mutations derived from Alzheimer's disease mapping to the catalytic subunit presenilin 1 (PS1). Here we report an atomic structure of human gamma-secretase at 3.4 A resolution, determined by single-particle cryo-electron microscopy. Mutations derived from Alzheimer's disease affect residues at two hotspots in PS1, each located at the centre of a distinct four transmembrane segment (TM) bundle. TM2 and, to a lesser extent, TM6 exhibit considerable flexibility, yielding a plastic active site and adaptable surrounding elements. The active site of PS1 is accessible from the convex side of the TM horseshoe, suggesting considerable conformational changes in nicastrin extracellular domain after substrate recruitment. Component protein APH-1 serves as a scaffold, anchoring the lone transmembrane helix from nicastrin and supporting the flexible conformation of PS1. Ordered phospholipids stabilize the complex inside the membrane. Our structure serves as a molecular basis for mechanistic understanding of gamma-secretase function.
-Authors: Bai, X., Yan, C., Yang, G., Lu, P., Ma, D., Sun, L., Zhou, R., Scheres, S.H.W., Shi, Y.
+An atomic structure of human gamma-secretase.,Bai XC, Yan C, Yang G, Lu P, Ma D, Sun L, Zhou R, Scheres SH, Shi Y Nature. 2015 Aug 17. doi: 10.1038/nature14892. PMID:26280335<ref>PMID:26280335</ref>
-Description: Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Lu, P]]
+<div class="pdbe-citations 5a63" style="background-color:#fffaf0;"></div>
-[[Category: Zhou, R]]
-[[Category: Yang, G]]
+==See Also==
-[[Category: Yan, C]]
+*[[Gamma secretase|Gamma secretase]]
-[[Category: Shi, Y]]
+== References ==
-[[Category: Bai, X]]
+<references/>
-[[Category: Ma, D]]
+__TOC__
-[[Category: Scheres, S.H.W]]
+</SX>
-[[Category: Sun, L]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bai X]]
+[[Category: Lu P]]
+[[Category: Ma D]]
+[[Category: Scheres SHW]]
+[[Category: Shi Y]]
+[[Category: Sun L]]
+[[Category: Yan C]]
+[[Category: Yang G]]
+[[Category: Zhou R]]