Dynamics of Lipid Transfer by Phosphatidylinositol Transfer Proteins in Cells
| Autor: | Shamshad Cockcroft, Patrick Ee, Sadaf Shadan, Nicolas Carvou, Roman Holic, Michelle Li, Judith Murray-Rust |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Golgi Apparatus Plasma protein binding Endoplasmic Reticulum Phosphatidylinositols Biochemistry PC12 Cells Cell membrane chemistry.chemical_compound 2 2'-Dipyridyl Cytosol Structural Biology Chlorocebus aethiops Disulfides Phospholipid Transfer Proteins lipid-binding cavity lipid exchange 0303 health sciences 030302 biochemistry & molecular biology Tryptophan Transport protein Cell biology Membrane docking Protein Transport medicine.anatomical_structure Ethylmaleimide COS Cells PtdIns transport Plant lipid transfer proteins Protein Binding HL-60 Cells Biology PITP domain Transfection 03 medical and health sciences PtdCho transport Genetics medicine Escherichia coli Animals Humans Phosphatidylinositol Molecular Biology Phosphatidylinositol transfer protein 030304 developmental biology Binding Sites Phospholipase C Cell Membrane Cell Biology Original Articles Rats chemistry Mutation |
| Zdroj: | Traffic (Copenhagen, Denmark) |
| ISSN: | 1600-0854 1398-9219 |
| Popis: | Of many lipid transfer proteins identified, all have been implicated in essential cellular processes, but the activity of none has been demonstrated in intact cells. Among these, phosphatidylinositol transfer proteins (PITP) are of particular interest as they can bind to and transfer phosphatidylinositol (PtdIns)--the precursor of important signalling molecules, phosphoinositides--and because they have essential functions in neuronal development (PITPalpha) and cytokinesis (PITPbeta). Structural analysis indicates that, in the cytosol, PITPs are in a 'closed' conformation completely shielding the lipid within them. But during lipid exchange at the membrane, they must transiently 'open'. To study PITP dynamics in intact cells, we chemically targeted their C95 residue that, although non-essential for lipid transfer, is buried within the phospholipid-binding cavity, and so, its chemical modification prevents PtdIns binding because of steric hindrance. This treatment resulted in entrapment of open conformation PITPs at the membrane and inactivation of the cytosolic pool of PITPs within few minutes. PITP isoforms were differentially inactivated with the dynamics of PITPbeta faster than PITPalpha. We identify two tryptophan residues essential for membrane docking of PITPs. |
| Databáze: | OpenAIRE |
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