Membrane fluidity adjusts the insertion of the transacylase PlsX to regulate phospholipid biosynthesis in Gram-positive bacteria
| العنوان: | Membrane fluidity adjusts the insertion of the transacylase PlsX to regulate phospholipid biosynthesis in Gram-positive bacteria |
|---|---|
| المؤلفون: | Diego de Mendoza, Beatriz Trastoy, Javier O. Cifuente, Frederico J. Gueiros-Filho, Marcos V.A.S. Navarro, Luis G.M. Basso, Xabier Contreras, Diego E. Sastre, Marcelo E. Guerin |
| المصدر: | J Biol Chem Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Membrane Fluidity, Phospholipid, Gram-Positive Bacteria, Biochemistry, Phosphates, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, Biosynthesis, Enterococcus faecalis, Escherichia coli, Membrane fluidity, Protein–lipid interaction, Molecular Biology, Phospholipids, 030102 biochemistry & molecular biology, Peripheral membrane protein, Cell Biology, Lipids, Enzyme structure, Cell biology, 030104 developmental biology, Membrane, chemistry, LIPÍDEOS, Acyltransferase, lipids (amino acids, peptides, and proteins), Bacillus subtilis |
| الوصف: | PlsX plays a central role in the coordination of fatty acid and phospholipid biosynthesis in Gram-positive bacteria. PlsX is a peripheral membrane acyltransferase that catalyzes the conversion of acyl-ACP to acyl-phosphate, which is in turn utilized by the polytopic membrane acyltransferase PlsY on the pathway of bacterial phospholipid biosynthesis. We have recently studied the interaction between PlsX and membrane phospholipids in vivo and in vitro, and observed that membrane association is necessary for the efficient transfer of acyl-phosphate to PlsY. However, understanding the molecular basis of such a channeling mechanism remains a major challenge. Here, we disentangle the binding and insertion events of the enzyme to the membrane, and the subsequent catalysis. We show that PlsX membrane binding is a process mostly mediated by phospholipid charge, whereas fatty acid saturation and membrane fluidity remarkably influence the membrane insertion step. Strikingly, the PlsX(L254E) mutant, whose biological functionality was severely compromised in vivo but remains catalytically active in vitro, was able to superficially bind to phospholipid vesicles, nevertheless, it loses the insertion capacity, strongly supporting the importance of membrane insertion in acyl-phosphate delivery. We propose a mechanism in which membrane fluidity governs the insertion of PlsX and thus regulates the biosynthesis of phospholipids in Gram-positive bacteria. This model may be operational in other peripheral membrane proteins with an unprecedented impact in drug discovery/development strategies. |
| تدمد: | 0021-9258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70c1b9d6e30b1a5b672186c1af785018 https://doi.org/10.1074/jbc.ra119.011122 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....70c1b9d6e30b1a5b672186c1af785018 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219258 |
|---|