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4upc

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== Function ==
== Function ==
[[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/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.
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== Publication Abstract from PubMed ==
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The gamma-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. Aberrant cleavage of the amyloid precursor protein (APP) results in aggregation of amyloid-beta, which accumulates in the brain and consequently causes Alzheimer's disease. Here we report the three-dimensional structure of an intact human gamma-secretase complex at 4.5 A resolution, determined by cryo-electron-microscopy single-particle analysis. The gamma-secretase complex comprises a horseshoe-shaped transmembrane domain, which contains 19 transmembrane segments (TMs), and a large extracellular domain (ECD) from nicastrin, which sits immediately above the hollow space formed by the TM horseshoe. Intriguingly, nicastrin ECD is structurally similar to a large family of peptidases exemplified by the glutamate carboxypeptidase PSMA. This structure serves as an important basis for understanding the functional mechanisms of the gamma-secretase complex.
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Three-dimensional structure of human gamma-secretase.,Lu P, Bai XC, Ma D, Xie T, Yan C, Sun L, Yang G, Zhao Y, Zhou R, Scheres SH, Shi Y Nature. 2014 Jun 29. doi: 10.1038/nature13567. PMID:25043039<ref>PMID:25043039</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
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<references/>
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</StructureSection>
</StructureSection>

Revision as of 06:30, 30 July 2014

Structure of a extracellular domain

4upc, resolution 5.40Å

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