Tian Xie;Chuangye Yan;Rui Zhou;Yanyu Zhao;Linfeng Sun;Guanghui Yang;Peilong Lu;Dan Ma;一公 施
Tsinghua University
发表时间:2014-9-16
期 刊:Proceedings of the National Academy of Sciences of the United States of America
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=84907228541&partnerID=8YFLogxK
γ-Secretase is an intramembrane protease responsible for the generation of amyloid-β (Aβ) peptides. Aberrant accumulation of Aβ 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 γ-secretase complex. No atomic-resolution structure had been identified on γ-secretase or any of its four components, hindering mechanistic understanding of γ-secretase function. Here we report the crystal structure of nicas-trin from Dictyostelium purpureum at 1.95-Å 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 hy-drophobic 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 γ-secretase complex.
Scopus度量
年份 | CiteScore | SJR | SNIP |
---|---|---|---|
1996 | |||
1997 | |||
1998 | |||
1999 | 8.52 | 2.398 | |
2000 | 7.927 | 2.452 | |
2001 | 7.189 | 2.458 | |
2002 | 7.281 | 2.498 | |
2003 | 7.129 | 2.507 | |
2004 | 7.197 | 2.617 | |
2005 | 6.94 | 2.546 | |
2006 | 6.849 | 2.45 | |
2007 | 6.867 | 2.46 | |
2008 | 7.034 | 2.431 | |
2009 | 7.025 | 2.552 | |
2010 | 6.898 | 2.541 | |
2011 | 16.8 | 6.864 | 2.632 |
2012 | 17.3 | 6.868 | 2.679 |
2013 | 17.4 | 7.073 | 2.721 |
2014 | 17.2 | 6.898 | 2.706 |
2015 | 17.8 | 6.814 | 2.664 |
2016 | 18 | 6.576 | 2.648 |
2017 | 17.1 | 6.092 | 2.655 |
2018 | 16.1 | 5.601 | 2.598 |
2019 | 15.7 | 5.165 | 2.689 |
2020 | 15.6 |
相似文献推荐