2MRK
Fyn SH2 domain in complex with the natural inhibitory phosphotyrosine peptide
Summary for 2MRK
| Entry DOI | 10.2210/pdb2mrk/pdb |
| Related | 2mqi 2mrj |
| NMR Information | BMRB: 25082 |
| Descriptor | Tyrosine-protein kinase Fyn, C-terminal Tyrosine-protein kinase Fyn (2 entities in total) |
| Functional Keywords | phosphorylated peptide, fyn kinase, sh2 domain, src kinase, transferase |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cytoplasm: P06241 P06241 |
| Total number of polymer chains | 2 |
| Total formula weight | 12944.54 |
| Authors | Huculeci, R.,Buts, L.,Lenaerts, A.J.,van Nuland, N. (deposition date: 2014-07-09, release date: 2015-07-15, Last modification date: 2024-11-20) |
| Primary citation | Huculeci, R.,Cilia, E.,Lyczek, A.,Buts, L.,Houben, K.,Seeliger, M.A.,van Nuland, N.,Lenaerts, T. Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking Its Activity. Structure, 24:1947-1959, 2016 Cited by PubMed Abstract: Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role in the activation process. Here, we show through experimental methyl dynamic results and predicted changes in side-chain conformational couplings that the SH2 structure of Fyn contains a dynamic network capable of propagating binding information. We reveal that binding the phosphorylated tail of Fyn perturbs a residue cluster near the linker connecting the SH2 and SH3 domains of Fyn, which is known to be relevant in the regulation of the activity of Fyn. Biochemical perturbation experiments validate that those residues are essential for inhibition of Fyn, leading to a gain of function upon mutation. These findings reveal how side-chain dynamics may facilitate the allosteric regulation of the different members of the Src kinase family. PubMed: 27692963DOI: 10.1016/j.str.2016.08.016 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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