Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding
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Renu Batra-Safferling
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 Å 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.
©2010 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- REVIEW
- Hexose-6-phosphate dehydrogenase in the endoplasmic reticulum
- GENES AND NUCLEIC ACIDS
- Biochemical characterization of human Ecdysoneless reveals a role in transcriptional regulation
- PROTEIN STRUCTURE AND FUNCTION
- Bovine β-lactoglobulin acts as an acid-resistant drug carrier by exploiting its diverse binding regions
- Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding
- A fluorescence correlation spectroscopy study of ligand interaction with cytokinin-specific binding protein from mung bean
- The oxygen-independent coproporphyrinogen III oxidase HemN utilizes harderoporphyrinogen as a reaction intermediate during conversion of coproporphyrinogen III to protoporphyrinogen IX
- MEMBRANES, LIPIDS, GLYCOBIOLOGY
- Phytosphingosine kills Candida albicans by disrupting its cell membrane
- CELL BIOLOGY AND SIGNALING
- Dexamethasone-dependent versus -independent markers of epithelial to mesenchymal transition in primary hepatocytes
- PROTEOLYSIS
- Potential role of multiple members of the kallikrein-related peptidase family of serine proteases in activating latent TGFβ1 in semen
- Binding and activation of the human plasma kinin-forming system on the cell walls of Candida albicans and Candida tropicalis
- A novel matrix metalloprotease-like enzyme (karilysin) of the periodontal pathogen Tannerella forsythia ATCC 43037
- NOVEL TECHNIQUES
- CYP21-catalyzed production of the long-term urinary metandienone metabolite 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping
