Utsikt
Senior Member (Voting Rights)
Systematic analyses of lipid mobilization by human lipid transfer proteins
Abstract
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Lipid transfer proteins (LTPs) maintain the specialized lipid compositions of organellar membranes1,2. In humans, many LTPs are implicated in diseases3, but for the majority, the cargo and auxiliary lipids facilitating transfer remain unknown.
We have combined biochemical, lipidomic and computational methods to systematically characterize LTP-lipid complexes4 and measure how LTP gains of function affect cellular lipidomes.
We identified bound lipids for approximately half of the hundred LTPs analyzed, confirming known ligands, while discovering new ones across most LTP families. Gains in LTP function affected the cellular abundance of both their known and newly identified lipid ligands, indicating comparable functional relevance of the two ligand sets.
Using structural bioinformatics, we have characterized mechanisms contributing to lipid selectivity, identifying preferences based on head group or acyl chain.
We demonstrate some basic principles of how LTPs mobilise their ligands. They commonly interact with several classes of lipids and exhibit broad but selective preference, not only for particular head groups, but also for lipid species with shorter acyl chains containing one or two unsaturations, suggesting that only subsets of lipid species are efficiently mobilized.
The datasets represent a resource for further analysis in different cell types and states, such as those associated with pathologies.
Web | DOI | PDF | Nature (Paywall)
Titeca, Kevin; Chiapparino, Antonella; Hennrich, Marco L.; Türei, Dénes; Moqadam, Mahmoud; Talandashti, Reza; Cuveillier, Camille; van Ek, Larissa; Zukowska, Joanna; Triana, Sergio; Echelard, Florian; Nielsen, Inger Ødum; Foged, Mads Møller; Gehin, Charlotte; Olechnovic, Kliment; Grudinin, Sergei; Saez-Rodriguez, Julio; Alexandrov, Theodore; Maeda, Kenji; Reuter, Nathalie; Gavin, Anne-Claude
Abstract
Line breaks added
Lipid transfer proteins (LTPs) maintain the specialized lipid compositions of organellar membranes1,2. In humans, many LTPs are implicated in diseases3, but for the majority, the cargo and auxiliary lipids facilitating transfer remain unknown.
We have combined biochemical, lipidomic and computational methods to systematically characterize LTP-lipid complexes4 and measure how LTP gains of function affect cellular lipidomes.
We identified bound lipids for approximately half of the hundred LTPs analyzed, confirming known ligands, while discovering new ones across most LTP families. Gains in LTP function affected the cellular abundance of both their known and newly identified lipid ligands, indicating comparable functional relevance of the two ligand sets.
Using structural bioinformatics, we have characterized mechanisms contributing to lipid selectivity, identifying preferences based on head group or acyl chain.
We demonstrate some basic principles of how LTPs mobilise their ligands. They commonly interact with several classes of lipids and exhibit broad but selective preference, not only for particular head groups, but also for lipid species with shorter acyl chains containing one or two unsaturations, suggesting that only subsets of lipid species are efficiently mobilized.
The datasets represent a resource for further analysis in different cell types and states, such as those associated with pathologies.
Web | DOI | PDF | Nature (Paywall)