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2mfq

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NMR solution structures of FRS2a PTB domain with neurotrophin receptor TrkB

Structural highlights

2mfq is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FRS2_HUMAN Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.^[1] ^[2]

Publication Abstract from PubMed

The fibroblast growth factor substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2alpha proteins interact with RTKs through the phosphotyrosine-binding domain (PTB) and transfer signals from the activated receptors to downstream effector proteins. Here, we report the NMR structure of the FRS2alpha PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2alpha-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either non-phosphorylated 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 FRS2alpha PTB domain. (c) Proteins 2014;. (c) 2014 Wiley Periodicals, Inc.

Structural insights into FRS2alpha PTB domain recognition by neurotrophin receptor TrkB.,Zeng L, Kuti M, Mujtaba S, Zhou MM Proteins. 2014 Jan 27. doi: 10.1002/prot.24523. PMID:24470253^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu Y, Chen Z, Ullrich A. EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2. Biol Chem. 2003 Aug;384(8):1215-26. PMID:12974390 doi:http://dx.doi.org/10.1515/BC.2003.134
↑ Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011 Jul 15;30(16):3259-73. doi: 10.1038/emboj.2011.234. PMID:21765395 doi:10.1038/emboj.2011.234
↑ Zeng L, Kuti M, Mujtaba S, Zhou MM. Structural insights into FRS2alpha PTB domain recognition by neurotrophin receptor TrkB. Proteins. 2014 Jan 27. doi: 10.1002/prot.24523. PMID:24470253 doi:http://dx.doi.org/10.1002/prot.24523