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
PMID: 8961927
Abstract:
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
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(+).
enzyme binding Interacting selectively and non-covalently with any enzyme.
protein complex binding Interacting selectively and non-covalently with any protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Biological process:
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.
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.
leukocyte migration The movement of a leukocyte within or between different tissues and organs of the body.
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).
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.
Cellular component:
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.
Structural annotations of the participating protein chains.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)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Chain A:
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).
Chain B:
The SH3 domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00018). A solved monomeric structure of the domain is represented by PDB ID 1nyf.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). The structure can be rotated by left click and hold anywhere on the structure. Representation options can be edited by right clicking on the structure window.
