Protein Interactions among Fe65, the Low-Density Lipoprotein Receptor-Related Protein, and the Amyloid Precursor Protein

被引:8
作者
Mulvihill, Melinda M. [1 ]
Guttman, Miklos [1 ]
Komives, Elizabeth A. [1 ]
机构
[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
NITRIC-OXIDE SYNTHASE; KAPPA-B-ALPHA; ADAPTER PROTEIN; CYTOPLASMIC DOMAIN; TYROSINE PHOSPHORYLATION; INTRACELLULAR DOMAIN; BINDING; RECOGNITION; PEPTIDE; COMPLEX;
D O I
10.1021/bi200508f
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta 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.
引用
收藏
页码:6208 / 6216
页数:9
相关论文
共 41 条
[1]   Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid [J].
Ando, K ;
Iijima, K ;
Elliott, JI ;
Kirino, Y ;
Suzuki, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (43) :40353-40361
[2]   v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1 [J].
Barnes, H ;
Ackermann, EJ ;
van der Geer, P .
ONCOGENE, 2003, 22 (23) :3589-3597
[3]   Thermodynamics reveal that helix four in the NLS of NF-κB p65 anchors IκBα, forming a very stable complex [J].
Bergqvist, Simon ;
Croy, Carrie H. ;
Kjaergaard, Magnus ;
Huxford, Tom ;
Ghosh, Gourisankar ;
Komives, Elizabeth A. .
JOURNAL OF MOLECULAR BIOLOGY, 2006, 360 (02) :421-434
[4]   Structural and functional consequences of tyrosine phosphorylation in the LRP1 cytoplasmic domain [J].
Betts, Gina N. ;
van der Geer, Peter ;
Komives, Elizabeth A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (23) :15656-15664
[5]  
Borg JP, 1996, MOL CELL BIOL, V16, P6229
[6]   Platelet-derived growth factor mediates tyrosine phosphorylation of the cytoplasmic domain of the low density lipoprotein receptor-related protein in caveolae [J].
Boucher, P ;
Liu, PS ;
Gotthardt, M ;
Hiesberger, T ;
Anderson, RGW ;
Herz, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (18) :15507-15513
[7]   A transcriptively active complex of APP with Fe65 and histone acetyltransferase Tip60 [J].
Cao, XW ;
Südhof, TC .
SCIENCE, 2001, 293 (5527) :115-120
[8]   Dissection of amyloid-β precursor protein-dependent transcriptional transactivation [J].
Cao, XW ;
Südhof, TC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (23) :24601-24611
[9]   Biophysical characterization of the free IκBα ankyrin repeat domain in solution [J].
Croy, CH ;
Bergqvist, S ;
Huxford, T ;
Ghosh, G ;
Komives, EA .
PROTEIN SCIENCE, 2004, 13 (07) :1767-1777
[10]   Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor [J].
Eck, MJ ;
DhePaganon, S ;
Trub, T ;
Nolte, RT ;
Shoelson, SE .
CELL, 1996, 85 (05) :695-705