Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis.
Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis.
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DOI：
10.1038/s41598-021-85195-5
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发表时间：
2021-03-11
影响因子：
4.6
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Cho G;Lee E;Kim J
磷脂酰乙醇胺（PE）是细胞膜的主要组成部分，在大多数细菌中仅由膜锚定磷脂酰丝氨酸脱羧酶（PSD）合成。该酶经历自动切割以活化，并利用异戊酰部分与PS形成席夫碱中间体以促进脱羧。然而，PSD指导的自成熟，PS结合和脱羧过程的结构基础仍不清楚。在这里，我们提出了X-射线晶体结构的PSD从大肠杆菌，代表一个载脂蛋白形式和PE结合的复合物，其中的磷脂是化学共轭的必要的乙酰基残基，模仿席夫碱中间体。PE复合PSD的高分辨率结构清楚地说明了与磷脂的脂肪酰基链的广泛疏水相互作用，提供了对广泛的细胞PS的酶的广泛特异性的见解。此外，这些结构强烈主张酶在脂质双层环境中的独特拓扑结构，其中酶通过由三个两亲性螺旋组成的N-末端结构域以单调的方式与细胞膜相关联。最后，突变分析表明，E.大肠杆菌PSD主要利用D90/D142-H144-S254实现酶原成熟的自动切割，其中D90和D142相互互补。
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.
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DOI：
10.1016/j.bbalip.2004.09.007
发表时间：
2004-11-08
影响因子：
4.8
作者：
Bürgermeister, M;Birner-Grünberger, R;Daum, G
通讯作者：
Daum, G
DOI：
10.1016/0005-2736(86)90237-3
发表时间：
1986-11-17
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
DENKINS, YM;SCHROIT, AJ
通讯作者：
SCHROIT, AJ
影响因子：
3.6
作者：
Chen, Ying-Lien;Montedonico, Anthony E.;Reynolds, Todd B.
通讯作者：
Reynolds, Todd B.
影响因子：
3.1
作者：
Davis, Sarah E.;Tams, Robert N.;Reynolds, Todd B.
通讯作者：
Reynolds, Todd B.
影响因子：
4.8
作者：
Choi, Jae-Yeon;Duraisingh, Manoj T.;Voelker, Dennis R.
通讯作者：
Voelker, Dennis R.