View source for 4r12


==Crystal structure of the gamma-secretase component Nicastrin==
<StructureSection load='4r12' size='340' side='right'caption='[[4r12]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4r12]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dictyostelium_purpureum Dictyostelium purpureum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R12 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4r12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r12 OCA], [https://pdbe.org/4r12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r12 RCSB], [https://www.ebi.ac.uk/pdbsum/4r12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r12 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NICA_DICPU NICA_DICPU] 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 (amyloid-beta precursor protein).[UniProtKB:Q92542]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
gamma-Secretase is an intramembrane protease responsible for the generation of amyloid-beta (Abeta) peptides. Aberrant accumulation of Abeta leads to the formation of amyloid plaques in the brain of patients with Alzheimer's disease. Nicastrin is the putative substrate-recruiting component of the gamma-secretase complex. No atomic-resolution structure had been identified on gamma-secretase or any of its four components, hindering mechanistic understanding of gamma-secretase function. Here we report the crystal structure of nicastrin from Dictyostelium purpureum at 1.95-A resolution. The extracellular domain of nicastrin contains a large lobe and a small lobe. The large lobe of nicastrin, thought to be responsible for substrate recognition, associates with the small lobe through a hydrophobic pivot at the center. The putative substrate-binding pocket is shielded from the small lobe by a lid, which blocks substrate entry. These structural features suggest a working model of nicastrin function. Analysis of nicastrin structure provides insights into the assembly and architecture of the gamma-secretase complex.

Crystal structure of the gamma-secretase component nicastrin.,Xie T, Yan C, Zhou R, Zhao Y, Sun L, Yang G, Lu P, Ma D, Shi Y Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13349-54. doi:, 10.1073/pnas.1414837111. Epub 2014 Sep 2. PMID:25197054<ref>PMID:25197054</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4r12" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gamma secretase|Gamma secretase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dictyostelium purpureum]]
[[Category: Large Structures]]
[[Category: Lu P]]
[[Category: Ma D]]
[[Category: Shi Y]]
[[Category: Sun L]]
[[Category: Xie T]]
[[Category: Yan C]]
[[Category: Yang G]]
[[Category: Zhao Y]]
[[Category: Zhou R]]