Recent developments on the studies of human memapsin 2 (beta-secretase)
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Published on: January 25, 2018
Jordan Tang1, Xiangyang He, Xianping Huang
1Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma University Health Science Center, Oklahoma City, OK 73104, USA. Jordan-Tang@omrf.ouhsc.edu
Abstract:
Several specific topics on recent findings in the studies of memapsin 2 (beta-secretase) are discussed in this article. New structural evidence on memapsin 2 has pointed to the structural basis of flap opening. Such a mechanism is thought to participate in the substrate sequence selection during the cellular function. Another potentially important area is the intracellular transport of memapsin 2. Here we discuss the involvement of APP in memapsin 2 endocytosis and the GGA proteins in recycling the protease back to the cell surface. These mechanisms may be connected with the cellular regulation of neuronal activity through the regulation of memapsin 2 activity and Abeta production.
Insights
Memapsin 2 (beta-secretase) structural studies reveal flap opening mechanisms for substrate selection. Intracellular transport involving APP and GGA proteins regulates neuronal activity and Abeta production.
Area of Science:
- Biochemistry
- Neuroscience
- Structural Biology
Background:
- Memapsin 2 (beta-secretase) plays a critical role in amyloid precursor protein (APP) processing.
- Understanding memapsin 2 function is crucial for neurodegenerative disease research.
Purpose of the Study:
- To discuss recent findings on memapsin 2 structure and function.
- To explore the mechanisms of memapsin 2 intracellular transport and its implications.
Main Methods:
- Analysis of new structural evidence of memapsin 2.
- Discussion of the roles of APP and GGA proteins in memapsin 2 trafficking.
Main Results:
- New structural data elucidate the flap opening mechanism of memapsin 2, crucial for substrate recognition.
- APP mediates memapsin 2 endocytosis, while GGA proteins facilitate its recycling to the cell surface.
Conclusions:
- Memapsin 2 flap dynamics are key to its substrate specificity.
- Intracellular trafficking pathways involving APP and GGA proteins link memapsin 2 activity to neuronal regulation and Abeta generation.
