TY  - JOUR
AU  - Batra-Safferling, R.
AU  - Granzin, J.
AU  - Moedder, S.
AU  - Hoffmann, S.
AU  - Willbold, D.
TI  - Structural studies of PI3K SH3 domain in complex with a peptide ligand: role of anchor residue in ligand binding
JO  - Biological chemistry
VL  - 391
SN  - 1431-6730
CY  - Berlin [u.a.]
PB  - de Gruyter
M1  - PreJuSER-9746
SP  - 33 - 42
PY  - 2010
N1  - The authors wish to thank Georg Buldt for continuous generous support. Furthermore, technical assistance by Esther Jonas and the beamline scientists at the ESRF (Grenoble, France) is acknowledged. We also thank Oliver Weiergraber for critical reading of the manuscript. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 575, B11) to D.W.
AB  - Src homology 3 (SH3) domains are mediators of protein-protein interactions. They comprise approximately 60 amino acid residues and are found in many intracellular signaling proteins. Here, we present the crystal structure of the SH3 domain from phosphatidylinositol 3-kinase (PI3K) in complex with the 12-residue proline-rich peptide PD1R (HSKRPLPPLPSL). The crystal structure of the PI3K SH3-PD1R complex at a resolution of 1.7 A reveals type I ligand orientation of the bound peptide with an extended conformation where the central portion forms a left-handed type II polyproline (PPII) helix. The overall structure of the SH3 domain shows minimal changes on ligand binding. In addition, we also attempted crystallization with another peptide ligand (PD1) where the residue at anchor position P(-3) is a tyrosine. The crystals obtained did not contain the PD1 ligand; instead, the ligand binding site is partially occupied by residues Arg18 and Trp55 from the symmetry-related PI3K SH3 molecule. Considering these crystal structures of PI3K SH3 together with published reports, we provide a comparative analysis of protein-ligand interactions that has helped us identify the individual residues which play an important role in defining target specificity.
KW  - Amino Acid Sequence
KW  - Binding Sites
KW  - Crystallography, X-Ray
KW  - Ligands
KW  - Models, Molecular
KW  - Molecular Sequence Data
KW  - Oligopeptides: metabolism
KW  - Peptides: chemistry
KW  - Phosphatidylinositol 3-Kinases: chemistry
KW  - Phosphatidylinositol 3-Kinases: metabolism
KW  - Protein Binding
KW  - src Homology Domains: physiology
KW  - Ligands (NLM Chemicals)
KW  - Oligopeptides (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - histidyl-seryl-lysyl-arginyl-prolyl-leucyl-prolyl-prolyl-leucyl-prolyl-seryl-leucine (NLM Chemicals)
KW  - polyproline (NLM Chemicals)
KW  - Phosphatidylinositol 3-Kinases (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19919182
UR  - <Go to ISI:>//WOS:000273206000004
DO  - DOI:10.1515/bc.2010.003
UR  - https://juser.fz-juelich.de/record/9746
ER  -