3ua7

Crystal Structure of the Human Fyn SH3 domain in complex with a peptide from the Hepatitis C virus NS5A-protein

spinqualitylabelsall models 3ua7, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ua7 is a 6 chain structure with sequence from Hepacivirus hominis and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: ACE, CL, FMT, GOL, NA, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FYN_HUMAN Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. Publication Abstract from PubMed The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc-binding phosphoprotein that plays an important role in viral RNA replication and is involved in altering signal transduction pathways in the host cell. This protein interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The 1.5 A resolution crystal structure of a complex between the SH3 domain of the Fyn tyrosine kinase and the C-terminal proline-rich motif of the NS5A-derived peptide APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl(2) and belonged to the tetragonal space group P4(1)2(1)2. The asymmetric unit is composed of four SH3 domains and two NS5A peptide molecules; only three of the domain molecules contain a bound peptide, while the fourth molecule seems to correspond to a free form of the domain. Additionally, two of the SH3 domains are bound to the same peptide chain and form a ternary complex. The proline-rich motif present in the NS5A protein seems to be important for RNA replication and virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the NS5A C-terminal proline-rich peptide found in this crystallographic structure may be important in the virus infection cycle. The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein.,Martin-Garcia JM, Luque I, Ruiz-Sanz J, Camara-Artigas A Acta Crystallogr D Biol Crystallogr. 2012 Aug;68(Pt 8):1030-40. Epub 2012 Jul 17. PMID:22868769 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine kinase 3D structures

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