Kinniment-Williams, Bethan, Jurgeleviciute, Vytaute, West, Daniel et al. (4 more authors) (2025) Structural unification of diverse transmembrane acyltransferases reveals a conserved fold for the Transmembrane Acyl Transferase (TmAT) superfamily. Journal of Biological Chemistry. 110546. ISSN: 1083-351X
Abstract
The movement of acyl groups across biological membranes is essential for many cellular processes. One major family of proteins catalysing this reaction are the acyl transferase family 3 (AT3) proteins, which form a pore to allow acyl-CoA to penetrate the membrane for transfer onto an extracytosolic acceptor molecule. Recent structures of the sequence-unrelated human heparan-α-glucosaminide N-acetyltransferase (HGSNAT) support a similar transmembrane acyl-group transfer mechanism. Here we demonstrate that both protein families contain a conserved 10-transmembrane helical fold with high structural and detectable sequence conservation around the acyl-CoA pore, supporting the previously proposed Transmembrane Acyl Transferase (TmAT) protein superfamily. In addition, we identify TmAT proteins, including the human Golgi sialate-O-acetyltransferase (CASD1), the human/fungal PIG-W/GWT1 enzymes and the bacterial vancomycin resistance protein VanTG, where the TmAT domain's function has been largely unrecognised. We conclude that the TmAT fold represents an ancient architecture for transmembrane acyl-group transfer with important roles in the dynamic modification of glycans in diverse processes across the three domains of life.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | ©2025 The Authors |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Sep 2025 11:10 |
Last Modified: | 20 Sep 2025 02:26 |
Published Version: | https://doi.org/10.1016/j.jbc.2025.110546 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.jbc.2025.110546 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:231105 |
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