Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors

Christophe Dhalluin, Kelley S. Yan, Olga Plotnikova, Kyung W. Lee, Lei Zeng, Miklos Kuti, Shiraz Mujtaba, Mitchell P. Goldfarb, Ming Ming Zhou

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the β sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal β strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation.

Original languageEnglish
Pages (from-to)921-929
Number of pages9
JournalMolecular Cell
Volume6
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

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