A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
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A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins. / Bolla, Jani Reddy; Corey, Robin A.; Sahin, Cagla; Gault, Joseph; Hummer, Alissa; Hopper, Jonathan T. S.; Lane, David P.; Drew, David; Allison, Timothy M.; Stansfeld, Phillip J.; Robinson, Carol V.; Landreh, Michael.
In: Angewandte Chemie - International Edition, Vol. 59, No. 9, 2020, p. 3523-3528.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
AU - Bolla, Jani Reddy
AU - Corey, Robin A.
AU - Sahin, Cagla
AU - Gault, Joseph
AU - Hummer, Alissa
AU - Hopper, Jonathan T. S.
AU - Lane, David P.
AU - Drew, David
AU - Allison, Timothy M.
AU - Stansfeld, Phillip J.
AU - Robinson, Carol V.
AU - Landreh, Michael
PY - 2020
Y1 - 2020
N2 - Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non-specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid-binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent-resistant lipids bound at the dimer interface in the leucine transporter show decreased koff rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid-II results in the formation of a 1:1 protein–lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution.
AB - Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non-specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid-binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent-resistant lipids bound at the dimer interface in the leucine transporter show decreased koff rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid-II results in the formation of a 1:1 protein–lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution.
KW - lipid binding
KW - membrane protein structure
KW - molecular dynamics
KW - native mass spectrometry
U2 - 10.1002/anie.201914411
DO - 10.1002/anie.201914411
M3 - Journal article
C2 - 31886601
AN - SCOPUS:85078676975
VL - 59
SP - 3523
EP - 3528
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
SN - 1433-7851
IS - 9
ER -
ID: 236316282