Structural highlights
Disease
[NICA_HUMAN] Hidradenitis suppurativa. The disease is caused by mutations affecting the gene represented in this entry.
Function
[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.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu P, Bai XC, Ma D, Xie T, Yan C, Sun L, Yang G, Zhao Y, Zhou R, Scheres SH, Shi Y. Three-dimensional structure of human gamma-secretase. Nature. 2014 Jun 29. doi: 10.1038/nature13567. PMID:25043039 doi:http://dx.doi.org/10.1038/nature13567
