Unknown

Dataset Information

0

Protein interactions among Fe65, the low-density lipoprotein receptor-related protein, and the amyloid precursor protein.


ABSTRACT: The adapter protein Fe65 has been proposed to be the link between the intracellular domains of the amyloid precursor protein, APP (AICD), and the low-density lipoprotein receptor-related protein (LRP-CT). Functional linkage between these two proteins has been established, and mutations within LRP-CT affect the amount of A? produced from APP. Previous work showed that AICD binds to protein interaction domain 2 (PID2) of Fe65. Although the structure of PID1 was determined recently, all attempts to demonstrate LRP-CT binding to this domain failed. We used biophysical experiments and binding studies to investigate the binding among these three proteins. Full-length Fe65 bound more weakly to AICD than did N-terminally truncated forms; however, the intramolecular domain-domain interactions that had been proposed to inhibit binding could not be observed using amide H-D exchange. Surprisingly, when LRP-CT is phosphorylated at Tyr4507, it bound to Fe65 PID1 despite the fact that this domain belongs to the Dab-like subclass of PIDs that are not supposed to be phosphorylation-dependent. Mutation of a critical arginine abolished binding, providing further proof of the phosphorylation dependence. Fe65 PID1 thus provides a link between the Dab-like class and the IRS-like class of PIDs and is the first Dab-like family member to show phosphorylation-dependent binding.

SUBMITTER: Mulvihill MM 

PROVIDER: S-EPMC3139566 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Protein interactions among Fe65, the low-density lipoprotein receptor-related protein, and the amyloid precursor protein.

Mulvihill Melinda M MM   Guttman Miklos M   Komives Elizabeth A EA  

Biochemistry 20110624 28


The adapter protein Fe65 has been proposed to be the link between the intracellular domains of the amyloid precursor protein, APP (AICD), and the low-density lipoprotein receptor-related protein (LRP-CT). Functional linkage between these two proteins has been established, and mutations within LRP-CT affect the amount of Aβ produced from APP. Previous work showed that AICD binds to protein interaction domain 2 (PID2) of Fe65. Although the structure of PID1 was determined recently, all attempts to  ...[more]

Similar Datasets

| S-EPMC3188680 | biostudies-literature
| S-EPMC327153 | biostudies-literature
2012-05-21 | E-GEOD-32145 | biostudies-arrayexpress
2012-05-22 | GSE32145 | GEO
| S-EPMC6156287 | biostudies-literature
| S-EPMC3859418 | biostudies-literature
| S-EPMC3272839 | biostudies-literature
| S-EPMC6497734 | biostudies-literature
| S-EPMC5622059 | biostudies-literature
| S-EPMC1383510 | biostudies-literature