2. Academic Validation
  3. The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3

The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3

  • Nat Commun. 2021 Nov 25;12(1):6869. doi: 10.1038/s41467-021-27244-1.
Qing Zhang  # 1,  Deqiang Yao  # 2 3,  Bing Rao  # 2 4,  Liyan Jian 2 4,  Yang Chen 2,  Kexin Hu 2,  Ying Xia 2 4,  Shaobai Li 2,  Yafeng Shen 2,  An Qin 4,  Jie Zhao 4,  Lu Zhou 5,  Ming Lei 2,  Xian-Cheng Jiang 6,  Yu Cao 7 8
Affiliations

Affiliations

  • 1 CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 333 Haike Road, Shanghai, 201210, China.
  • 2 Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, Shanghai, 200125, China.
  • 3 State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
  • 4 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
  • 5 Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • 6 Department of Cell Biology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA.
  • 7 Institute of Precision Medicine, the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 115 Jinzun Road, Shanghai, 200125, China. [email protected].
  • 8 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. [email protected].
  • # Contributed equally.
PMID: 34824256 DOI: 10.1038/s41467-021-27244-1
Abstract

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.

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