Interaction of Presenilin-1 C-terminal fragment with FKBP38
The gene product of familial Alzheimer’s disease, presenilin-1 (PS-1), is a polytopic protein consisting of eight transmembrane domains and is predominantly localized in the endoplasmic reticulum (ER) and Golgi apparatus. Previous studies have shown that FK506 binding protein 38 is the direct intera...
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| Format: | Theses and Dissertations |
| Published: |
2008
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| Online Access: | http://hdl.handle.net/10356/6572 |
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| Institution: | Nanyang Technological University |
| Summary: | The gene product of familial Alzheimer’s disease, presenilin-1 (PS-1), is a polytopic protein consisting of eight transmembrane domains and is predominantly localized in the endoplasmic reticulum (ER) and Golgi apparatus. Previous studies have shown that FK506 binding protein 38 is the direct interacting partner of PS-1 C-terminal fragment (CTF) and the interaction promotes apoptosis by reducing mitochondrial Bcl-2. Nevertheless, the binding interface remains unclear. Here we demonstrate that the C-terminal half of the cytoplasmic loop region of PS-1 CTF can be co-immunoprecipitated with FKBP38. The co-localization study and Fluorescent Resonance Energy Transfer (FRET) assay further validate their interaction at cellular level. And we further narrow down the binding interface to be within residues 350 to 417. The structural study of the PS-1 loop region suggests its flexible and disordered characteristic. Moreover, co-expression of the identified binding domain on PS-1 CTF with FKBP38 promotes the redistribution of FKBP38 from mitochondria to ER. And this PS-1 CTF fragment retains its pro-apoptotic function as the full length PS-1 CTF. |
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