Identification and assessment of cardiolipin interactions with E. coli inner membrane proteins

TY - JOUR

T1 - Identification and assessment of cardiolipin interactions with E. coli inner membrane proteins

AU - Corey, Robin A.

AU - Song, Wanling

AU - Duncan, Anna L.

AU - Ansell, T. Bertie

AU - Sansom, Mark S.P.

AU - Stansfeld, Phillip J.

N1 - Publisher Copyright: © 2021 The Authors.

PY - 2021/8

Y1 - 2021/8

N2 - Integral membrane proteins are localized and/or regulated by lipids present in the surrounding bilayer. While bacteria have relatively simple membranes, there is ample evidence that many bacterial proteins bind to specific lipids, especially the anionic lipid cardiolipin. Here, we apply molecular dynamics simulations to assess lipid binding to 42 different Escherichia coli inner membrane proteins. Our data reveal an asymmetry between the membrane leaflets, with increased anionic lipid binding to the inner leaflet regions of the proteins, particularly for cardiolipin. From our simulations, we identify >700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. This allows us to construct a set of metrics for defining a high-affinity cardiolipin binding site on bacterial membrane proteins, paving the way for a heuristic approach to defining other protein-lipid interactions.

AB - Integral membrane proteins are localized and/or regulated by lipids present in the surrounding bilayer. While bacteria have relatively simple membranes, there is ample evidence that many bacterial proteins bind to specific lipids, especially the anionic lipid cardiolipin. Here, we apply molecular dynamics simulations to assess lipid binding to 42 different Escherichia coli inner membrane proteins. Our data reveal an asymmetry between the membrane leaflets, with increased anionic lipid binding to the inner leaflet regions of the proteins, particularly for cardiolipin. From our simulations, we identify >700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. This allows us to construct a set of metrics for defining a high-affinity cardiolipin binding site on bacterial membrane proteins, paving the way for a heuristic approach to defining other protein-lipid interactions.

UR - http://www.scopus.com/inward/record.url?scp=85112779300&partnerID=8YFLogxK

U2 - 10.1126/sciadv.abh2217

DO - 10.1126/sciadv.abh2217

M3 - Journal article

C2 - 34417182

AN - SCOPUS:85112779300

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

IS - 34

M1 - eabh2217

ER -