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Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB
Author(s) -
Zeng Lei,
Kuti Miklos,
Mujtaba Shiraz,
Zhou MingMing
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24523
Subject(s) - fibroblast growth factor receptor , receptor tyrosine kinase , low affinity nerve growth factor receptor , tropomyosin receptor kinase b , microbiology and biotechnology , cancer research , chemistry , fibroblast growth factor , signal transduction , receptor , biology , biochemistry , neurotrophin , neurotrophic factors
The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine‐binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α‐PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. Proteins 2014; 82:1534–1541. © 2014 Wiley Periodicals, Inc.