The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3.
1-Acylglycerophosphocholine O-Acyltransferase
/ chemistry
Acyl Coenzyme A
/ chemistry
Acylation
Animals
Catalytic Domain
Chickens
Cryoelectron Microscopy
Crystallography, X-Ray
Lysophosphatidylcholines
/ chemistry
Models, Molecular
Phospholipids
/ chemistry
Protein Multimerization
Structure-Activity Relationship
Substrate Specificity
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 11 2021
25 11 2021
Historique:
received:
15
07
2021
accepted:
08
11
2021
entrez:
26
11
2021
pubmed:
27
11
2021
medline:
31
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34824256
doi: 10.1038/s41467-021-27244-1
pii: 10.1038/s41467-021-27244-1
pmc: PMC8617236
doi:
Substances chimiques
Acyl Coenzyme A
0
Lysophosphatidylcholines
0
Phospholipids
0
arachidonyl-coenzyme A
17046-56-9
1-Acylglycerophosphocholine O-Acyltransferase
EC 2.3.1.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6869Informations de copyright
© 2021. The Author(s).
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