Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain.
We applied a novel application of FLIM-FRET to in situ measurement and quantification of protein interactions to explore isoform specific differences in Aβ-ApoE interaction and ApoE tertiary conformation in senile plaques in human Alzheimer brain. ApoE3 interacts more closely with Aβ than ApoE4, but...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a075653211154ded91f8cb220fe6a7ec |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a075653211154ded91f8cb220fe6a7ec |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a075653211154ded91f8cb220fe6a7ec2021-11-18T06:59:33ZApolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain.1932-620310.1371/journal.pone.0014586https://doaj.org/article/a075653211154ded91f8cb220fe6a7ec2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21297948/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We applied a novel application of FLIM-FRET to in situ measurement and quantification of protein interactions to explore isoform specific differences in Aβ-ApoE interaction and ApoE tertiary conformation in senile plaques in human Alzheimer brain. ApoE3 interacts more closely with Aβ than ApoE4, but a greater proportion of Aβ molecules within plaques are decorated with ApoE4 than ApoE3, lending strong support to the hypothesis that isoform specific differences in ApoE are linked with Aβ deposition. We found an increased number of ApoE N-terminal fragments in ApoE4 plaques, consistent with the observation that ApoE4 is more easily cleaved than ApoE3. In addition, we measured a small but significant isoform specific difference in ApoE domain interaction. Based on our in situ data, supported by traditional biochemical data, we propose a pathway by which isoform specific conformational differences increase the level of cleavage at the hinge region of ApoE4, leading to a loss of ApoE function to mediate clearance of Aβ and thereby increase the risk of AD for carriers of the APOEε4 allele.Phillip B JonesKenneth W AdamsAnete RozkalneTara L Spires-JonesTammy T HshiehTadafumi HashimotoChristine A F von ArminMathew MielkeBrian J BacskaiBradley T HymanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14586 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Phillip B Jones Kenneth W Adams Anete Rozkalne Tara L Spires-Jones Tammy T Hshieh Tadafumi Hashimoto Christine A F von Armin Mathew Mielke Brian J Bacskai Bradley T Hyman Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain. |
| description |
We applied a novel application of FLIM-FRET to in situ measurement and quantification of protein interactions to explore isoform specific differences in Aβ-ApoE interaction and ApoE tertiary conformation in senile plaques in human Alzheimer brain. ApoE3 interacts more closely with Aβ than ApoE4, but a greater proportion of Aβ molecules within plaques are decorated with ApoE4 than ApoE3, lending strong support to the hypothesis that isoform specific differences in ApoE are linked with Aβ deposition. We found an increased number of ApoE N-terminal fragments in ApoE4 plaques, consistent with the observation that ApoE4 is more easily cleaved than ApoE3. In addition, we measured a small but significant isoform specific difference in ApoE domain interaction. Based on our in situ data, supported by traditional biochemical data, we propose a pathway by which isoform specific conformational differences increase the level of cleavage at the hinge region of ApoE4, leading to a loss of ApoE function to mediate clearance of Aβ and thereby increase the risk of AD for carriers of the APOEε4 allele. |
| format |
article |
| author |
Phillip B Jones Kenneth W Adams Anete Rozkalne Tara L Spires-Jones Tammy T Hshieh Tadafumi Hashimoto Christine A F von Armin Mathew Mielke Brian J Bacskai Bradley T Hyman |
| author_facet |
Phillip B Jones Kenneth W Adams Anete Rozkalne Tara L Spires-Jones Tammy T Hshieh Tadafumi Hashimoto Christine A F von Armin Mathew Mielke Brian J Bacskai Bradley T Hyman |
| author_sort |
Phillip B Jones |
| title |
Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain. |
| title_short |
Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain. |
| title_full |
Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain. |
| title_fullStr |
Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain. |
| title_full_unstemmed |
Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-β in human Alzheimer brain. |
| title_sort |
apolipoprotein e: isoform specific differences in tertiary structure and interaction with amyloid-β in human alzheimer brain. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/a075653211154ded91f8cb220fe6a7ec |
| work_keys_str_mv |
AT phillipbjones apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT kennethwadams apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT aneterozkalne apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT taralspiresjones apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT tammythshieh apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT tadafumihashimoto apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT christineafvonarmin apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT mathewmielke apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT brianjbacskai apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain AT bradleythyman apolipoproteineisoformspecificdifferencesintertiarystructureandinteractionwithamyloidbinhumanalzheimerbrain |
| _version_ |
1718424122405421056 |