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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Main Author: Tai, Jeff Seng Thong
Other Authors: Yoon, Ho Sup
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
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spelling sg-ntu-dr.10356-65722023-02-28T18:37:03Z Interaction of Presenilin-1 C-terminal fragment with FKBP38 Tai, Jeff Seng Thong Yoon, Ho Sup School of Biological Sciences DRNTU::Science::Biological sciences 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. ​Master of Science 2008-09-17T11:42:02Z 2008-09-17T11:42:02Z 2007 2007 Thesis http://hdl.handle.net/10356/6572 Nanyang Technological University application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Tai, Jeff Seng Thong
Interaction of Presenilin-1 C-terminal fragment with FKBP38
description 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.
author2 Yoon, Ho Sup
author_facet Yoon, Ho Sup
Tai, Jeff Seng Thong
format Theses and Dissertations
author Tai, Jeff Seng Thong
author_sort Tai, Jeff Seng Thong
title Interaction of Presenilin-1 C-terminal fragment with FKBP38
title_short Interaction of Presenilin-1 C-terminal fragment with FKBP38
title_full Interaction of Presenilin-1 C-terminal fragment with FKBP38
title_fullStr Interaction of Presenilin-1 C-terminal fragment with FKBP38
title_full_unstemmed Interaction of Presenilin-1 C-terminal fragment with FKBP38
title_sort interaction of presenilin-1 c-terminal fragment with fkbp38
publishDate 2008
url http://hdl.handle.net/10356/6572
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