Crystal structure of the ARF-GAP domain and ankyrin repeats of PYK2-associated protein beta
| Autor: | Valsan Mandiyan, Stevan R. Hubbard, Julian Andreev, Joseph Schlessinger |
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| Rok vydání: | 1999 |
| Předmět: |
Ankyrins
Models Molecular Repetitive Sequences Amino Acid ADP ribosylation factor Molecular Sequence Data Sequence alignment Biology Crystallography X-Ray Catalysis Protein Structure Secondary General Biochemistry Genetics and Molecular Biology SH3 domain src Homology Domains Protein structure Computer Graphics Ankyrin Amino Acid Sequence Molecular Biology chemistry.chemical_classification Sequence Homology Amino Acid General Immunology and Microbiology ADP-Ribosylation Factors General Neuroscience Protein-Tyrosine Kinases Recombinant Proteins Cell biology Pleckstrin homology domain Kinetics Focal Adhesion Kinase 2 Biochemistry chemistry Mutagenesis Site-Directed Ankyrin repeat Ras superfamily Sequence Alignment Research Article |
| Zdroj: | The EMBO Journal. 18:6890-6898 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/18.24.6890 |
| Popis: | ADP ribosylation factors (ARFs), which are members of the Ras superfamily of GTP-binding proteins, are critical components of vesicular trafficking pathways in eukaryotes. Like Ras, ARFs are active in their GTP-bound form, and their duration of activity is controlled by GTPase-activating proteins (GAPs), which assist ARFs in hydrolyzing GTP to GDP. PAPbeta, a protein that binds to and is phosphorylated by the non-receptor tyrosine kinase PYK2, contains several modular signaling domains including a pleckstrin homology domain, an SH3 domain, ankyrin repeats and an ARF-GAP domain. Sequences of ARF-GAP domains show no recognizable similarity to those of other GAPs, and contain a characteristic Cys-X(2)-Cys-X(16-17)-Cys-X(2)-Cys motif. The crystal structure of the PAPbeta ARF-GAP domain and the C-terminal ankyrin repeats has been determined at 2.1 A resolution. The ARF-GAP domain comprises a central three-stranded beta-sheet flanked by five alpha-helices, with a Zn(2+) ion coordinated by the four cysteines of the cysteine-rich motif. Four ankyrin repeats are also present, the first two of which form an extensive interface with the ARF-GAP domain. An invariant arginine and several nearby hydrophobic residues are solvent exposed and are predicted to be the site of interaction with ARFs. Site-directed mutagenesis of these residues confirms their importance in ARF-GAP activity. |
| Databáze: | OpenAIRE |
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