Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis

Abstract Phosphatidylethanolamine (PE), a major component of the cellular membrane across all domains of life, is synthesized exclusively by membrane-anchored phosphatidylserine decarboxylase (PSD) in most bacteria. The enzyme undergoes auto-cleavage for activation and utilizes the pyruvoyl moiety t...

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Autores principales:	Gyuhyeok Cho, Eunju Lee, Jungwook Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa40a587449749c59ad801977fdc1277
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spelling	oai:doaj.org-article:aa40a587449749c59ad801977fdc12772021-12-02T13:33:44ZStructural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis10.1038/s41598-021-85195-52045-2322https://doaj.org/article/aa40a587449749c59ad801977fdc12772021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85195-5https://doaj.org/toc/2045-2322Abstract Phosphatidylethanolamine (PE), a major component of the cellular membrane across all domains of life, is synthesized exclusively by membrane-anchored phosphatidylserine decarboxylase (PSD) in most bacteria. The enzyme undergoes auto-cleavage for activation and utilizes the pyruvoyl moiety to form a Schiff base intermediate with PS to facilitate decarboxylation. However, the structural basis for self-maturation, PS binding, and decarboxylation processes directed by PSD remain unclear. Here, we present X-ray crystal structures of PSD from Escherichia coli, representing an apo form and a PE-bound complex, in which the phospholipid is chemically conjugated to the essential pyruvoyl residue, mimicking the Schiff base intermediate. The high-resolution structures of PE-complexed PSD clearly illustrate extensive hydrophobic interactions with the fatty acyl chains of the phospholipid, providing insights into the broad specificity of the enzyme over a wide range of cellular PS. Furthermore, these structures strongly advocate the unique topology of the enzyme in a lipid bilayer environment, where the enzyme associates with cell membranes in a monotopic fashion via the N-terminal domain composed of three amphipathic helices. Lastly, mutagenesis analyses reveal that E. coli PSD primarily employs D90/D142–H144–S254 to achieve auto-cleavage for the proenzyme maturation, where D90 and D142 act in complementary to each other.Gyuhyeok ChoEunju LeeJungwook KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gyuhyeok Cho Eunju Lee Jungwook Kim Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
description	Abstract Phosphatidylethanolamine (PE), a major component of the cellular membrane across all domains of life, is synthesized exclusively by membrane-anchored phosphatidylserine decarboxylase (PSD) in most bacteria. The enzyme undergoes auto-cleavage for activation and utilizes the pyruvoyl moiety to form a Schiff base intermediate with PS to facilitate decarboxylation. However, the structural basis for self-maturation, PS binding, and decarboxylation processes directed by PSD remain unclear. Here, we present X-ray crystal structures of PSD from Escherichia coli, representing an apo form and a PE-bound complex, in which the phospholipid is chemically conjugated to the essential pyruvoyl residue, mimicking the Schiff base intermediate. The high-resolution structures of PE-complexed PSD clearly illustrate extensive hydrophobic interactions with the fatty acyl chains of the phospholipid, providing insights into the broad specificity of the enzyme over a wide range of cellular PS. Furthermore, these structures strongly advocate the unique topology of the enzyme in a lipid bilayer environment, where the enzyme associates with cell membranes in a monotopic fashion via the N-terminal domain composed of three amphipathic helices. Lastly, mutagenesis analyses reveal that E. coli PSD primarily employs D90/D142–H144–S254 to achieve auto-cleavage for the proenzyme maturation, where D90 and D142 act in complementary to each other.
format	article
author	Gyuhyeok Cho Eunju Lee Jungwook Kim
author_facet	Gyuhyeok Cho Eunju Lee Jungwook Kim
author_sort	Gyuhyeok Cho
title	Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
title_short	Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
title_full	Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
title_fullStr	Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
title_full_unstemmed	Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
title_sort	structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aa40a587449749c59ad801977fdc1277
work_keys_str_mv	AT gyuhyeokcho structuralinsightsintophosphatidylethanolamineformationinbacterialmembranebiogenesis AT eunjulee structuralinsightsintophosphatidylethanolamineformationinbacterialmembranebiogenesis AT jungwookkim structuralinsightsintophosphatidylethanolamineformationinbacterialmembranebiogenesis
_version_	1718392874234544128

Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis

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