Fe65-PTB2 dimerization mimics Fe65-APP interaction
Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AIC...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 May 2017
|
| In: |
Frontiers in molecular neuroscience
Year: 2017, Volume: 10 |
| ISSN: | 1662-5099 |
| DOI: | 10.3389/fnmol.2017.00140 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3389/fnmol.2017.00140 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fnmol.2017.00140/full 
|
| Author Notes: | Lukas P. Feilen, Kevin Haubrich, Paul Strecker, Sabine Probst, Simone Eggert, Gunter Stier, Irmgard Sinning, Uwe Konietzko, Stefan Kins, Bernd Simon and Klemens Wild |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1580776639 | ||
| 003 | DE-627 | ||
| 005 | 20220815003519.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180907s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fnmol.2017.00140 |2 doi | |
| 035 | |a (DE-627)1580776639 | ||
| 035 | |a (DE-576)510776639 | ||
| 035 | |a (DE-599)BSZ510776639 | ||
| 035 | |a (OCoLC)1341018163 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Feilen, Lukas Peter |e VerfasserIn |0 (DE-588)1166450325 |0 (DE-627)1030428808 |0 (DE-576)510775659 |4 aut | |
| 245 | 1 | 0 | |a Fe65-PTB2 dimerization mimics Fe65-APP interaction |c Lukas P. Feilen, Kevin Haubrich, Paul Strecker, Sabine Probst, Simone Eggert, Gunter Stier, Irmgard Sinning, Uwe Konietzko, Stefan Kins, Bernd Simon and Klemens Wild |
| 264 | 1 | |c 11 May 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 07.09.2018 | ||
| 520 | |a Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal alpha-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling. | ||
| 650 | 4 | |a AICD | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a amyloid precursor protein (APP) | |
| 650 | 4 | |a FE65 | |
| 650 | 4 | |a Homodimerization | |
| 650 | 4 | |a phosphotyrosine-binding domain (PTB) | |
| 700 | 1 | |a Haubrich, Kevin |d 1991- |e VerfasserIn |0 (DE-588)1166450910 |0 (DE-627)1030429316 |0 (DE-576)510776442 |4 aut | |
| 700 | 1 | |a Stier, Gunter |e VerfasserIn |0 (DE-588)1164406019 |0 (DE-627)1028857144 |0 (DE-576)508520622 |4 aut | |
| 700 | 1 | |a Sinning, Irmgard |d 1960- |e VerfasserIn |0 (DE-588)1027598617 |0 (DE-627)72945133X |0 (DE-576)166290580 |4 aut | |
| 700 | 1 | |a Wild, Klemens |e VerfasserIn |0 (DE-588)1049291190 |0 (DE-627)781602394 |0 (DE-576)177410892 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in molecular neuroscience |d Lausanne : Frontiers Research Foundation, 2008 |g 10(2017) Artikel-Nummer 140, 12 Seiten |h Online-Ressource |w (DE-627)579826449 |w (DE-600)2452967-9 |w (DE-576)286502267 |x 1662-5099 |7 nnas |a Fe65-PTB2 dimerization mimics Fe65-APP interaction |
| 773 | 1 | 8 | |g volume:10 |g year:2017 |a Fe65-PTB2 dimerization mimics Fe65-APP interaction |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fnmol.2017.00140 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fnmol.2017.00140/full |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180907 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 1049291190 |a Wild, Klemens |m 1049291190:Wild, Klemens |d 700000 |d 711000 |e 700000PW1049291190 |e 711000PW1049291190 |k 0/700000/ |k 1/700000/711000/ |p 11 |y j | ||
| 998 | |g 1027598617 |a Sinning, Irmgard |m 1027598617:Sinning, Irmgard |d 700000 |d 711000 |d 700000 |d 718000 |e 700000PS1027598617 |e 711000PS1027598617 |e 700000PS1027598617 |e 718000PS1027598617 |k 0/700000/ |k 1/700000/711000/ |k 0/700000/ |k 1/700000/718000/ |p 7 | ||
| 998 | |g 1164406019 |a Stier, Gunter |m 1164406019:Stier, Gunter |d 700000 |d 711000 |e 700000PS1164406019 |e 711000PS1164406019 |k 0/700000/ |k 1/700000/711000/ |p 6 | ||
| 998 | |g 1166450910 |a Haubrich, Kevin |m 1166450910:Haubrich, Kevin |d 700000 |d 711000 |e 700000PH1166450910 |e 711000PH1166450910 |k 0/700000/ |k 1/700000/711000/ |p 2 | ||
| 998 | |g 1166450325 |a Feilen, Lukas |m 1166450325:Feilen, Lukas |d 700000 |d 711000 |e 700000PF1166450325 |e 711000PF1166450325 |k 0/700000/ |k 1/700000/711000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1580776639 |e 3024949208 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"doi":["10.3389/fnmol.2017.00140"],"eki":["1580776639"]},"title":[{"title_sort":"Fe65-PTB2 dimerization mimics Fe65-APP interaction","title":"Fe65-PTB2 dimerization mimics Fe65-APP interaction"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedKey":"2017","dateIssuedDisp":"11 May 2017"}],"relHost":[{"part":{"year":"2017","volume":"10","text":"10(2017) Artikel-Nummer 140, 12 Seiten"},"language":["eng"],"pubHistory":["2008 -"],"note":["Gesehen am 04.06.20"],"disp":"Fe65-PTB2 dimerization mimics Fe65-APP interactionFrontiers in molecular neuroscience","type":{"media":"Online-Ressource","bibl":"periodical"},"name":{"displayForm":["Frontiers Research Foundation"]},"recId":"579826449","physDesc":[{"extent":"Online-Ressource"}],"id":{"zdb":["2452967-9"],"eki":["579826449"],"issn":["1662-5099"]},"title":[{"title":"Frontiers in molecular neuroscience","title_sort":"Frontiers in molecular neuroscience"}],"origin":[{"dateIssuedDisp":"2008-","publisher":"Frontiers Research Foundation","publisherPlace":"Lausanne","dateIssuedKey":"2008"}]}],"name":{"displayForm":["Lukas P. Feilen, Kevin Haubrich, Paul Strecker, Sabine Probst, Simone Eggert, Gunter Stier, Irmgard Sinning, Uwe Konietzko, Stefan Kins, Bernd Simon and Klemens Wild"]},"language":["eng"],"note":["Gesehen am 07.09.2018"],"person":[{"given":"Lukas Peter","display":"Feilen, Lukas Peter","family":"Feilen","role":"aut"},{"role":"aut","family":"Haubrich","display":"Haubrich, Kevin","given":"Kevin"},{"display":"Stier, Gunter","given":"Gunter","role":"aut","family":"Stier"},{"given":"Irmgard","display":"Sinning, Irmgard","family":"Sinning","role":"aut"},{"display":"Wild, Klemens","given":"Klemens","family":"Wild","role":"aut"}],"recId":"1580776639"} | ||
| SRT | |a FEILENLUKAFE65PTB2DI1120 | ||