ArticleThe EMBO journal2004
Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains.
Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 107 citations in OpenAlex.
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- Membrane binding of endocytic myosin-1s is inhibited by a class of ankyrin repeat proteins.bioRxiv : the preprint server for biology · 2023Article
- Structural basis for activation of Arf1 at the Golgi complex.Cell reports · 2022Article
- Systematic simulation of the interactions of pleckstrin homology domains with membranes.Science advances · 2022Article
- Kinase-independent synthesis of 3-phosphorylated phosphoinositides by a phosphotransferase.Nature cell biology · 2022Article
- An update on genetically encoded lipid biosensors.Molecular biology of the cell · 2022Article
- Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids.Structure (London, England : 1993) · 2021Article
- Quantification of Genetically Encoded Lipid Biosensors.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Monitoring Phosphoinositide Fluxes and Effectors During Leukocyte Chemotaxis and Phagocytosis.Frontiers in cell and developmental biology · 2021Review
- Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes.Science advances · 2020Article
- Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes.Structure (London, England : 1993) · 2019Article
- Ancient complement and lineage-specific evolution of the Sec7 ARF GEF proteins in eukaryotes.Molecular biology of the cell · 2019Article
- ARF GTPases and their GEFs and GAPs: concepts and challenges.Molecular biology of the cell · 2019Review
- A high-avidity biosensor reveals plasma membrane PI(3,4)PThe Journal of cell biology · 2019Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The pleckstrin homology (PH) domains of the homologous proteins Grp1 (general receptor for phosphoinositides), ARNO (Arf nucleotide binding site opener), and Cytohesin-1 bind phosphatidylinositol (PtdIns) 3,4,5-trisphosphate with unusually high selectivity. Remarkably, splice variants that differ only by the insertion of a single glycine residue in the beta1/beta2 loop exhibit dual specificity for PtdIns(3,4,5)P(3) and PtdIns(4,5)P(2). The structural basis for this dramatic specificity switch is not apparent from the known modes of phosphoinositide recognition. Here, we report crystal structures for dual specificity variants of the Grp1 and ARNO PH domains in either the unliganded form or in complex with the head groups of PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3). Loss of contacts with the beta1/beta2 loop with no significant change in head group orientation accounts for the significant decrease in PtdIns(3,4,5)P(3) affinity observed for the dual specificity variants. Conversely, a small increase rather than decrease in affinity for PtdIns(4,5)P(2) is explained by a novel binding mode, in which the glycine insertion alleviates unfavorable interactions with the beta1/beta2 loop. These observations are supported by a systematic mutational analysis of the determinants of phosphoinositide recognition.
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