1A0N

NMR STUDY OF THE SH3 DOMAIN FROM FYN PROTO-ONCOGENE TYROSINE KINASE COMPLEXED WITH THE SYNTHETIC PEPTIDE P2L CORRESPONDING TO RESIDUES 91-104 OF THE P85 SUBUNIT OF PI3-KINASE, FAMILY OF 25 STRUCTURES

Summary for 1A0N

• Entry DOI: 10.2210/pdb1a0n/pdb
• Descriptor: PRO-PRO-ARG-PRO-LEU-PRO-VAL-ALA-PRO-GLY-SER-SER-LYS-THR, FYN (2 entities in total)
• Functional Keywords: complex (phosphotransferase-peptide), sh3 domain, polyproline-binding, complex (phosphotransferase-peptide) complex, complex (phosphotransferase/peptide)
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane: P06241
• Total number of polymer chains: 2
• Total formula weight: 9103.88

Authors

Renzoni, D.A.,Pugh, D.J.R.,Siligardi, G.,Das, P.,Morton, C.J.,Rossi, C.,Waterfield, M.D.,Campbell, I.D.,Ladbury, J.E. (deposition date: 1997-12-05, release date: 1998-02-25, Last modification date: 2024-05-22)

Primary citation

Renzoni, D.A.,Pugh, D.J.,Siligardi, G.,Das, P.,Morton, C.J.,Rossi, C.,Waterfield, M.D.,Campbell, I.D.,Ladbury, J.E.
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.
Biochemistry, 35:15646-15653, 1996

PubMed 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.

PubMed: 8961927
DOI: 10.1021/bi9620969

Experimental method

SOLUTION NMR