scholarly journals The Electrostatic Basis of Diacylglycerol Pyrophosphate—Protein Interaction

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 290
Author(s):  
Zachary Graber ◽  
Desmond Owusu Kwarteng ◽  
Shannon M. Lange ◽  
Yannis Koukanas ◽  
Hady Khalifa ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Protein Interaction ◽  
Anionic Phospholipid ◽  
Tryptophan Residues ◽  
Switch Mechanism ◽  
31P Mas Nmr ◽  
Calcium And Magnesium ◽  
Ionic Binding ◽  
Novel Model ◽  
Positively Charged

Diacylglycerol pyrophosphate (DGPP) is an anionic phospholipid formed in plants, yeast, and parasites under multiple stress stimuli. It is synthesized by the phosphorylation action of phosphatidic acid (PA) kinase on phosphatidic acid, a signaling lipid with multifunctional properties. PA functions in the membrane through the interaction of its negatively charged phosphomonoester headgroup with positively charged proteins and ions. DGPP, like PA, can interact electrostatically via the electrostatic-hydrogen bond switch mechanism but differs from PA in its overall charge and shape. The formation of DGPP from PA alters the physicochemical properties as well as the structural dynamics of the membrane. This potentially impacts the molecular and ionic binding of cationic proteins and ions with the DGPP enriched membrane. However, the results of these important interactions in the stress response and in DGPP’s overall intracellular function is unknown. Here, using 31P MAS NMR, we analyze the effect of the interaction of low DGPP concentrations in model membranes with the peptides KALP23 and WALP23, which are flanked by positively charged Lysine and neutral Tryptophan residues, respectively. Our results show a significant effect of KALP23 on the charge of DGPP as compared to WALP23. There was, however, no significant effect on the charge of the phosphomonoester of DGPP due to the interaction with positively charged lipids, dioleoyl trimethylammonium propane (DOTAP) and dioleoyl ethyl-phosphatidylcholine (EtPC). Divalent calcium and magnesium cations induce deprotonation of the DGPP headgroup but showed no noticeable differences on DGPP’s charge. Our results lead to a novel model for DGPP—protein interaction.

scholarly journals Extension of the Scope of Anionic Phospholipid-Based Nanoformulation to Kaempferol and Indometacin

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110026
Author(s):  
Noriyuki Uchida ◽  
Masayoshi Yanagi ◽  
Kei Shimoda ◽  
Hiroki Hamada
Keyword(s):  
Phosphatidic Acid ◽  
Anionic Phospholipid ◽  
Anionic Phospholipids ◽  
Dispersion Agent

In this work, resveratrol was dispersed with anionic phospholipids of 1,2-dipalmitoyl-sn-glycero-3-phosphorylglycerol (DPPG), 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, and 1,2-distearoyl-sn-glycero-3-phosphoglycerol. Moreover, small-sized nanoparticles of kaempferol and indometacin were successfully prepared by using DPPG as a dispersion agent.

scholarly journals Lipin 2 Binds Phosphatidic Acid by the Electrostatic Hydrogen Bond Switch Mechanism Independent of Phosphorylation

2014 ◽  
Vol 289 (26) ◽  
pp. 18055-18066 ◽  
Author(s):  
James M. Eaton ◽  
Sankeerth Takkellapati ◽  
Robert T. Lawrence ◽  
Kelley E. McQueeney ◽  
Salome Boroda ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Phosphatidic Acid ◽  
Switch Mechanism

Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation

2008 ◽  
Vol 414 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Xinjiang Wang ◽  
Yuji Shi ◽  
Junru Wang ◽  
Guochang Huang ◽  
Xuejun Jiang
Keyword(s):  
Protein Interaction ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Ww Domains ◽  
Protein Protein Interaction ◽  
Cellular Analysis ◽  
C Terminus ◽  
Tryptophan Residues ◽  
Interaction Domains ◽  
Phosphatase And Tensin Homologue

PTEN (phosphatase and tensin homologue deleted on chromosome 10), a potent tumour suppressor and multifunctional signalling protein, is under intricate regulation. In the present study, we have investigated the mechanism and regulation of PTEN ubiquitination catalysed by NEDD4-1 (neural-precursor-cell-expressed, developmentally down-regulated 4-1), a ubiquitin ligase for PTEN we identified recently. Using the reconstituted assay and cellular analysis, we demonstrated that NEDD4-1-mediated PTEN ubiquitination depends on its intact HECT (homologous to E6-associated protein C-terminus) domain. Instead of using its WW domains (protein–protein interaction domains containing two conserved tryptophan residues) as a protein interaction module, NEDD4-1 interacts with PTEN through its N-terminal region containing a C2 domain as well as the HECT domain. Strikingly, we found that a C-terminal truncated PTEN fragment binds to NEDD4-1 with higher affinity than the full-length PTEN, suggesting an intrinsic inhibitory effect of the PTEN C-terminus on PTEN–NEDD4-1 interaction. Moreover, the C-terminal truncated PTEN is more sensitive to NEDD4-1-mediated ubiquitination and degradation. Therefore the present study reveals that the C-terminus of PTEN plays a critical role in stabilizing PTEN via antagonizing NEDD4-1-induced PTEN protein decay; conversely, truncation of the PTEN C-terminus results in rapid NEDD4-1-mediated PTEN degradation, a possible mechanism accounting for attenuation of PTEN function by certain PTEN mutations in human cancers.

scholarly journals Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein Interaction

2018 ◽  
Vol 72 (2) ◽  
pp. 328-340.e8 ◽  
Author(s):  
Han Han ◽  
Ruxi Qi ◽  
Jeff Jiajing Zhou ◽  
Albert Paul Ta ◽  
Bing Yang ◽  
...  
Keyword(s):  
Phosphatidic Acid ◽  
Protein Interaction ◽  
Hippo Pathway ◽  
Lipid Protein Interaction ◽  
The Hippo Pathway

scholarly journals The penetration of serum albumin into phospholipid monolayers of different fatty acid chain length and interfacial charge

1970 ◽  
Vol 119 (1) ◽  
pp. 21-25 ◽  
Author(s):  
P. Quinn ◽  
R. M. C. Dawson
Keyword(s):  
Fatty Acid ◽  
Phosphatidic Acid ◽  
Serum Albumin ◽  
Water Interface ◽  
Fatty Acid Chain ◽  
Phospholipid Monolayers ◽  
Oppositely Charged ◽  
Interfacial Charge ◽  
Positively Charged ◽  
Long Chain

1. The highest surface pressure of phosphatidylcholine monolayers allowing penetration of delipidated serum albumin decreased in the order dibehenoyl>distearoyl>dipalmitoyl=dimyristoyl. This pressure was not related to the area occupied or to the space available between the phospholipid molecules at the interface. 2. Penetration of albumin into yeast phosphatidylcholine monolayers was increased by adding a small percentage of long-chain anions (phosphatidic acid, dicetylphosphoric acid) to the film but only when the protein was below its isoelectric point (i.e. positively charged). 3. Stearylamine added to phosphatidylcholine monolayers had no effect on albumin penetration even when the protein was oppositely charged to that of the phospholipid/water interface. 4. The results are discussed in relation to the activation of certain phospholipases by anionic amphipathic substances.

scholarly journals Solid charged-core model of ball lightning

2010 ◽  
Vol 28 (1) ◽  
pp. 223-232 ◽  
Author(s):  
D. B. Muldrew
Keyword(s):  
Plasma Layer ◽  
Ball Lightning ◽  
Underlying Assumption ◽  
The Core ◽  
Electron Layer ◽  
Thin Electron ◽  
Em Field ◽  
A Charge ◽  
Novel Model ◽  
Positively Charged

Abstract. In this study, ball lightning (BL) is assumed to have a solid, positively-charged core. According to this underlying assumption, the core is surrounded by a thin electron layer with a charge nearly equal in magnitude to that of the core. A vacuum exists between the core and the electron layer containing an intense electromagnetic (EM) field which is reflected and guided by the electron layer. The microwave EM field applies a ponderomotive force (radiation pressure) to the electrons preventing them from falling into the core. The energetic electrons ionize the air next to the electron layer forming a neutral plasma layer. The electric-field distributions and their associated frequencies in the ball are determined by applying boundary conditions to a differential equation given by Stratton (1941). It is then shown that the electron and plasma layers are sufficiently thick and dense to completely trap and guide the EM field. This model of BL is exceptional in that it can explain all or nearly all of the peculiar characteristics of BL. The ES energy associated with the core charge can be extremely large which can explain the observations that occasionally BL contains enormous energy. The mass of the core prevents the BL from rising like a helium-filled balloon – a problem with most plasma and burning-gas models. The positively charged core keeps the negatively charged electron layer from diffusing away, i.e. it holds the ball together; other models do not have a mechanism to do this. The high electrical charges on the core and in the electron layer explains why some people have been electrocuted by BL. Experiments indicate that BL radiates microwaves upon exploding and this is consistent with the model. The fact that this novel model of BL can explain these and other observations is strong evidence that the model should be taken seriously.

scholarly journals Chemokines act as phosphatidylserine-bound “find-me” signals in apoptotic cell clearance

PLoS Biology ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. e3001259
Author(s):  
Sergio M. Pontejo ◽  
Philip M. Murphy
Keyword(s):  
Chemokine Receptors ◽  
Apoptotic Cell ◽  
Apoptotic Cells ◽  
Anionic Phospholipid ◽  
Anionic Phospholipids ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance ◽  
G Protein Coupled ◽  
Positively Charged

Removal of apoptotic cells is essential for maintenance of tissue homeostasis. Chemotactic cues termed “find-me” signals attract phagocytes toward apoptotic cells, which selectively expose the anionic phospholipid phosphatidylserine (PS) and other “eat-me” signals to distinguish healthy from apoptotic cells for phagocytosis. Blebs released by apoptotic cells can deliver find-me signals; however, the mechanism is poorly understood. Here, we demonstrate that apoptotic blebs generated in vivo from mouse thymus attract phagocytes using endogenous chemokines bound to the bleb surface. We show that chemokine binding to apoptotic cells is mediated by PS and that high affinity binding of PS and other anionic phospholipids is a general property of many but not all chemokines. Chemokines are positively charged proteins that also bind to anionic glycosaminoglycans (GAGs) on cell surfaces for presentation to leukocyte G protein–coupled receptors (GPCRs). We found that apoptotic cells down-regulate GAGs as they up-regulate PS on the cell surface and that PS-bound chemokines, unlike GAG-bound chemokines, are able to directly activate chemokine receptors. Thus, we conclude that PS-bound chemokines may serve as find-me signals on apoptotic vesicles acting at cognate chemokine receptors on leukocytes.

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