The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3

• Published in: Nature communications Vol. 12; no. 1; pp. 6869 - 11
• Main Authors: Zhang, Qing, Yao, Deqiang, Rao, Bing, Jian, Liyan, Chen, Yang, Hu, Kexin, Xia, Ying, Li, Shaobai, Shen, Yafeng, Qin, An, Zhao, Jie, Zhou, Lu, Lei, Ming, Jiang, Xian-Cheng, Cao, Yu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Acylglycerophosphocholine O-acyltransferase; 1-Acylglycerophosphocholine O-Acyltransferase - chemistry; 1-Acylglycerophosphocholine O-Acyltransferase - metabolism; 101/28; 631/45/287/1194; 631/535/1258/1259; 82/16; 82/29; 82/83; Acyl Coenzyme A - chemistry; Acyl Coenzyme A - metabolism; Acylation; Acyltransferase; Animals; Atherosclerosis; Biology; Catalytic Domain; Cell membranes; Chemical reactions; Chickens; Cryoelectron Microscopy; Crystal structure; Crystallography; Crystallography, X-Ray; Deacylation; Electron microscopy; Fluidity; Functional analysis; Humanities and Social Sciences; Laboratories; Lecithin; Lysophosphatidylcholine; Lysophosphatidylcholines - chemistry; Lysophosphatidylcholines - metabolism; Mammals; Medicine; Membrane fluidity; Membrane proteins; Metabolism; Microscopy; Models, Molecular; multidisciplinary; Musculoskeletal system; Phosphatidylcholine; Phospholipids; Phospholipids - chemistry; Phospholipids - metabolism; Protein Multimerization; Proteins; Receptors; Science; Science (multidisciplinary); Structure-Activity Relationship; Structure-function relationships; Substrate preferences; Substrate Specificity; Substrates; Tunnels; X-ray crystallography
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27244-1

As the major component of cell membranes, phosphatidylcholine (PC) is synthesized de novo in the Kennedy pathway and then undergoes extensive deacylation-reacylation remodeling via Lands’ cycle. The re-acylation is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT) and among the four LPCAT members in human, the LPCAT3 preferentially introduces polyunsaturated acyl onto the sn-2 position of lysophosphatidylcholine, thereby modulating the membrane fluidity and membrane protein functions therein. Combining the x-ray crystallography and the cryo-electron microscopy, we determined the structures of LPCAT3 in apo-, acyl donor-bound, and acyl receptor-bound states. A reaction chamber was revealed in the LPCAT3 structure where the lysophosphatidylcholine and arachidonoyl-CoA were positioned in two tunnels connected near to the catalytic center. A side pocket was found expanding the tunnel for the arachidonoyl CoA and holding the main body of arachidonoyl. The structural and functional analysis provides the basis for the re-acylation of lysophosphatidylcholine and the substrate preference during the reactions. During phosphatidylcholine (PC) remodeling re-acylation is catalyzed by lysophosphatidylcholine acyltransferases (LPCAT). Here, the authors present crystal and cryo-EM structures of chicken LPCAT3 in the apo-, acyl donor-bound and acyl receptor-bound states, and based on the structures and further functional analysis they discuss the mechanism of the enzyme.