Database Accession: DI1000165
Name: SH3 domain from Fyn complexed with the proline-rich binding site on the p85 subunit of PI3-kinase
PDB ID: 1a0n
Experimental method: NMR
Source organism: Homo sapiens
Proof of disorder:
Kd: 1.00×10-06 M
Primary publication of the structure:
Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE
Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase.
(1996) Biochemistry 35: 15646-53
The interaction of the Fyn SH3 domain with the p85 subunit of PI3-kinase is investigated using structural detail and thermodynamic data. The solution structure complex of the SH3 domain with a proline-rich peptide mimic of the binding site on the p85 subunit is described. This indicates that the peptide binds as a poly(L-proline) type II helix. Circular dichroism spectroscopic studies reveal that in the unbound state the peptide exhibits no structure. Thermodynamic data for the binding of this peptide to the SH3 domain suggest that the weak binding (approximately 31 microM) of this interaction is, in part, due to the entropically unfavorable effect of helix formation (delta S0 = -78 J.mol-1.K-1). Binding of the SH3 domain to the intact p85 subunit (minus its own SH3 domain) is tighter, and the entropic and enthalpic contributions are very different from those given by the peptide interaction (delta S0 = +252 J.mol-1.K-1; delta H0 = +44 kJ.mol-1). From these dramatically different thermodynamic measurements we are able to conclude that the interaction of the proline-rich peptide does not effectively mimic the interaction of the intact p85 subunit with the SH3 domain and suggest that other interactions could be important.
phosphatidylinositol 3-kinase binding Interacting selectively and non-covalently with a phosphatidylinositol 3-kinase, any enzyme that catalyzes the addition of a phosphate group to an inositol lipid at the 3' position of the inositol ring.
phosphatidylinositol-4,5-bisphosphate 3-kinase activity Catalysis of the reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + ATP = a 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + ADP + 2 H(+).
receptor binding Interacting selectively and non-covalently with one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
enzyme binding Interacting selectively and non-covalently with any enzyme.
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of phosphatidylinositol 3-kinase signaling Any process that modulates the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.
viral process A multi-organism process in which a virus is a participant. The other participant is the host. Includes infection of a host cell, replication of the viral genome, and assembly of progeny virus particles. In some cases the viral genetic material may integrate into the host genome and only subsequently, under particular circumstances, 'complete' its life cycle.
platelet activation A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
T cell costimulation The process of providing, via surface-bound receptor-ligand pairs, a second, antigen-independent, signal in addition to that provided by the T cell receptor to augment T cell activation.
Fc-gamma receptor signaling pathway involved in phagocytosis An Fc-gamma receptor signaling pathway that contributes to the endocytic engulfment of external particulate material by phagocytes.
interleukin-7-mediated signaling pathway A series of molecular signals initiated by the binding of interleukin-7 to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
phosphatidylinositol phosphorylation The process of introducing one or more phosphate groups into a phosphatidylinositol, any glycerophosphoinositol having one phosphatidyl group esterified to one of the hydroxy groups of inositol.
vascular endothelial growth factor receptor signaling pathway Any series of molecular signals initiated by the binding of an extracellular ligand to a vascular endothelial growth factor receptor (VEGFR) located on the surface of the receiving cell, and ending with regulation of a downstream cellular process, e.g. transcription.
phosphatidylinositol-mediated signaling A series of molecular signals in which a cell uses a phosphatidylinositol-mediated signaling to convert a signal into a response. Phosphatidylinositols include phosphatidylinositol (PtdIns) and its phosphorylated derivatives.
T cell receptor signaling pathway A series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
regulation of developmental process Any process that modulates the frequency, rate or extent of development, the biological process whose specific outcome is the progression of a multicellular organism over time from an initial condition (e.g. a zygote, or a young adult) to a later condition (e.g. a multicellular animal or an aged adult).
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA (for protein-coding genes) and the translation of that mRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.
positive regulation of cellular component organization Any process that activates or increases the frequency, rate or extent of a process involved in the formation, arrangement of constituent parts, or disassembly of cell structures, including the plasma membrane and any external encapsulating structures such as the cell wall and cell envelope.
positive regulation of signal transduction Any process that activates or increases the frequency, rate or extent of signal transduction.
regulation of phosphorylation Any process that modulates the frequency, rate or extent of addition of phosphate groups into a molecule.
negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
cellular response to peptide hormone stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.
regulation of intracellular protein transport Any process that modulates the frequency, rate or extent of the directed movement of proteins within cells.
regulation of protein localization to membrane
positive regulation of protein localization to nucleus Any process that activates or increases the frequency, rate or extent of protein localization to nucleus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
extrinsic component of membrane The component of a membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region.
Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: No modifications of the original PDB file.
Name: Phosphatidylinositol 3-kinase regulatory subunit alpha
Source organism: Homo sapiens
Length: 14 residues
Sequence:Sequence according to PDB SEQRESPPRPLPVAPGSSKT
UniProtKB AC: P27986 (positions: 91-104)Coverage: 1.9%
UniRef90 AC: UniRef90_P27986 (positions: 91-104)
Name: Tyrosine-protein kinase Fyn
Source organism: Homo sapiens
Length: 69 residues
Sequence:Sequence according to PDB SEQRESGSTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVDSIQAEE
UniProtKB AC: P06241 (positions: 80-148)Coverage: 12.8%
UniRef90 AC: UniRef90_P06241 (positions: 80-148)
Circular dichroism spectroscopic studies reveal that in the unbound state the peptide exhibits no structure (PMID: 8961927). The protein region involved in the interaction contains a known functional linear motif (LIG_SH3_1).
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