2MFQ

NMR solution structures of FRS2a PTB domain with neurotrophin receptor TrkB

Summary for 2MFQ

• Entry DOI: 10.2210/pdb2mfq/pdb
• NMR Information: BMRB: 19562
• Descriptor: Fibroblast growth factor receptor substrate 2, BDNF/NT-3 growth factors receptor (2 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Endomembrane system: Q8WU20; Cell membrane; Single-pass type I membrane protein: Q16620
• Total number of polymer chains: 2
• Total formula weight: 15994.93

Authors

Zeng, L.,Zhou, M. (deposition date: 2013-10-18, release date: 2014-03-05, Last modification date: 2024-11-06)

Primary citation

Zeng, L.,Kuti, M.,Mujtaba, S.,Zhou, M.M.
Structural insights into FRS2 alpha PTB domain recognition by neurotrophin receptor TrkB.
Proteins, 82:1534-1541, 2014

PubMed Abstract: 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.

PubMed: 24470253
DOI: 10.1002/prot.24523

Experimental method

SOLUTION NMR