Cryo-EM structures reveal the mechanism of phosphatidylserine remodeling by membrane-bound glycerophospholipid O-acyltransferase 1
- 1Memorial Sloan Kettering Cancer Center
Abstract
Lands cycle remodeling of glycerophospholipid acyl chains is crucial for cells to maintain appropriate membrane composition. Glycerophospholipids are cleaved at the glycerol sn2-position by phospholipase A. The lysophospholipids are reacylated by enzymes of the membrane-bound O-acyltransferase (MBOAT) family to incorporate specific fatty-acyl chains to adjust membrane properties. How MBOAT enzymes recognize specific acyl-CoA donors, select lysophospholipid acceptors, and release products is unclear. Phosphatidylserine (PS), a critical anionic phospholipid, controls membrane surface charge, signaling-protein recruitment, and cell-death-associated membrane recognition, and PS acyl-chain remodeling is linked to ferroptosis resistance. Here, we showed that MBOAT1 preferentially generates monounsaturated fatty acid-containing PS from lyso-PS. High-resolution cryo-electron microscopy structures of human MBOAT1 captured distinct binding poses of the fatty acyl donor, lyso-PS acceptor, and PS product. With lipidomics, enzymology and molecular dynamics simulations, these structures reveal the mechanism and pathway of MBOAT1-dependent PS remodeling.
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BibTeX
@misc{kim2026cryoem,
title = {{Cryo-EM structures reveal the mechanism of phosphatidylserine remodeling by membrane-bound glycerophospholipid O-acyltransferase 1}},
author = {L. Kim and S. Kim and R. Ly and L. Cohen-Abeles and P. Liu and X. Jiang and D. Kwon and R. V. Farese and T. C. Walther},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748671},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748671v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cryo-EM structures reveal the mechanism of phosphatidylserine remodeling by membrane-bound glycerophospholipid O-acyltransferase 1
AU - L. Kim
AU - S. Kim
AU - R. Ly
AU - L. Cohen-Abeles
AU - P. Liu
AU - X. Jiang
AU - D. Kwon
AU - R. V. Farese
AU - T. C. Walther
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748671
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748671v1
AB - Lands cycle remodeling of glycerophospholipid acyl chains is crucial for cells to maintain appropriate membrane composition. Glycerophospholipids are cleaved at the glycerol sn2-position by phospholipase A. The lysophospholipids are reacylated by enzymes of the membrane-bound O-acyltransferase (MBOAT) family to incorporate specific fatty-acyl chains to adjust membrane properties. How MBOAT enzymes recognize specific acyl-CoA donors, select lysophospholipid acceptors, and release products is unclear. Phosphatidylserine (PS), a critical anionic phospholipid, controls membrane surface charge, signaling-protein recruitment, and cell-death-associated membrane recognition, and PS acyl-chain remodeling is linked to ferroptosis resistance. Here, we showed that MBOAT1 preferentially generates monounsaturated fatty acid-containing PS from lyso-PS. High-resolution cryo-electron microscopy structures of human MBOAT1 captured distinct binding poses of the fatty acyl donor, lyso-PS acceptor, and PS product. With lipidomics, enzymology and molecular dynamics simulations, these structures reveal the mechanism and pathway of MBOAT1-dependent PS remodeling.
ER -