8z0n
From Proteopedia
Structure and dynamics of Drk-SH2 domain and its site-specific interaction with Sev
Structural highlights
FunctionGRAP_DROME Adapter protein which modulates signaling mediated by several receptor tyrosine kinases such as sev and Ack (PubMed:22615583, PubMed:8462097, PubMed:8462098). Required for proper signaling by sevenless (PubMed:8462097, PubMed:8462098). May act to stimulate the ability of Sos to catalyze Ras1 activation by linking sevenless and Sos in a signaling complex (PubMed:8462097, PubMed:8462098). Required for functional and morphological integrities of the scolopidia, sensory neurons and the antennal mechanosensory and motor center (AMMC) brain neuropil (PubMed:30610177). Required for Ack-dependent suppression of apoptosis in the eye (PubMed:22615583).[1] [2] [3] [4] Publication Abstract from PubMedThe Drosophila downstream receptor kinase (Drk), a homologue of human GRB2, participates in the signal transduction from the extracellular to the intracellular environment. Drk receives signals through the interaction of its Src homology 2 (SH2) domain with the phosphorylated tyrosine residue in the receptor tyrosine kinases (RTKs). Here, we present the solution NMR structure of the SH2 domain of Drk (Drk-SH2), which was determined in the presence of a phosphotyrosine (pY)-containing peptide derived from a receptor tyrosine kinase, Sevenless (Sev). The solution structure of Drk-SH2 possess a common SH2 domain architecture, consisting of three beta strands imposed between two alpha helices. Additionally, we interpret the site-specific interactions of the Drk-SH2 domain with the pY-containing peptide through NMR titration experiments. The dynamics of Drk-SH2 were also analysed through NMR-relaxation experiments as well as the molecular dynamic simulation. The docking simulations of the pY-containing peptide onto the protein surface of Drk-SH2 provided the orientation of the peptide, which showed a good agreement with the analysis of the SH2 domain of GRB2. Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase.,Sayeesh PM, Iguchi M, Inomata K, Ikeya T, Ito Y Int J Mol Sci. 2024 Jun 9;25(12):6386. doi: 10.3390/ijms25126386. PMID:38928093[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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