Structural Basis of 3-Phosphoinositide Recognition by Pleckstrin Homology Domains
| Autor: | Susan E. Lietzke, David G. Lambright, Thomas Charles Cronin, Jes K. Klarlund, Michael P. Czech, Sahana Bose, Anil Chawla |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Protein Conformation Inositol Phosphates Molecular Sequence Data Receptors Cytoplasmic and Nuclear GTPase Biology Crystallography X-Ray Phosphatidylinositols Protein Structure Secondary src Homology Domains Phosphatidylinositol 3-Kinases chemistry.chemical_compound Signaling proteins Pi Inositol Amino Acid Sequence Phosphatidylinositol Protein kinase A Molecular Biology Conserved Sequence Binding Sites Sequence Homology Amino Acid Cell Biology Recombinant Proteins Pleckstrin homology domain Amino Acid Substitution chemistry Biochemistry Second messenger system Mutagenesis Site-Directed Sequence Alignment |
| Zdroj: | Molecular Cell. 6(2):385-394 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(00)00038-1 |
| Popis: | Lipid second messengers generated by phosphoinositide (PI) 3-kinases regulate diverse cellular functions through interaction with pleckstrin homology (PH) domains in modular signaling proteins. The PH domain of Grp1, a PI 3-kinase-activated exchange factor for Arf GTPases, selectively binds phosphatidylinositol 3,4,5-trisphosphate with high affinity. We have determined the structure of the Grp1 PH domain in the unliganded form and bound to inositol 1,3,4,5-tetraphosphate. A novel mode of phosphoinositide recognition involving a 20-residue insertion within the β6/β7 loop explains the unusually high specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding typical of several PH domains including that of protein kinase B. When compared to other PH domains, general determinants of 3-phosphoinositide recognition and specificity can be deduced. |
| Databáze: | OpenAIRE |
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