TY  - JOUR
A1  - Radzimanowski, Jens
A1  - Ravaud, Stéphanie
A1  - Schlesinger, Sabine
A1  - Koch, Joachim
A1  - Beyreuther, Konrad
A1  - Sinning, Irmgard
A1  - Wild, Klemens
T1  - Crystal structure of the human Fe65-PTB1 domain
T2  - Journal of biological chemistry
N2  - The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The N-terminal PTB domain (Fe65-PTB1) was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. We have determined the crystal structures of human Fe65-PTB1 in its apo- and in a phosphate-bound form at 2.2 and 2.7A resolution, respectively. The overall fold shows a PTB-typical pleckstrin homology domain superfold. Although Fe65-PTB1 has been classified on an evolutionary basis as a Dab-like PTB domain, it contains attributes of other PTB domain subfamilies. The phosphotyrosine-binding pocket resembles IRS-like PTB domains, and the bound phosphate occupies the binding site of the phosphotyrosine (Tyr(P)) within the canonical NPXpY recognition motif. In addition Fe65-PTB1 contains a loop insertion between helix alpha2 and strand beta2(alpha2/beta2 loop) similar to members of the Shc-like PTB domain subfamily. The structural comparison with the Dab1-PTB domain reveals a putative phospholipid-binding site opposite the peptide binding pocket. We suggest Fe65-PTB1 to interact with its target proteins involved in translocation and signaling of APP in a phosphorylation-dependent manner.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76383
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-763832
SN  - 0021-9258
VL  - 283.2008
IS  - 34
SP  - 23113
EP  - 23120
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -