3I5R

PI3K SH3 domain in complex with a peptide ligand

Summary for 3I5R

• Entry DOI: 10.2210/pdb3i5r/pdb
• Related: 3I5S
• Descriptor: Phosphatidylinositol 3-kinase regulatory subunit alpha, Peptide ligand (3 entities in total)
• Functional Keywords: sh3 domain, peptide complex, alternative splicing, disease mutation, host-virus interaction, phosphoprotein, polymorphism, sh2 domain, ubl conjugation, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 10780.98

Authors

Batra-Safferling, R.,Granzin, J.,Modder, S.,Hoffmann, S.,Willbold, D. (deposition date: 2009-07-06, release date: 2010-03-02, Last modification date: 2023-09-06)

Primary citation

Batra-Safferling, R.,Granzin, J.,Modder, S.,Hoffmann, S.,Willbold, D.
Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding.
Biol.Chem., 391:33-42, 2010

PubMed Abstract: 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.

PubMed: 19919182
DOI: 10.1515/BC.2010.003

Experimental method

X-RAY DIFFRACTION (1.7 Å)