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  3. A Global Map of Lipid-Binding Proteins and Their Ligandability in Cells

A Global Map of Lipid-Binding Proteins and Their Ligandability in Cells

  • Cell. 2015 Jun 18;161(7):1668-80. doi: 10.1016/j.cell.2015.05.045.
Micah J Niphakis 1,  Kenneth M Lum 2,  Armand B Cognetta 3rd 2,  Bruno E Correia 2,  Taka-Aki Ichu 2,  Jose Olucha 2,  Steven J Brown 2,  Soumajit Kundu 2,  Fabiana Piscitelli 2,  Hugh Rosen 2,  Benjamin F Cravatt 3
Affiliations

Affiliations

  • 1 The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: [email protected].
  • 2 The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • 3 The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: [email protected].
PMID: 26091042 DOI: 10.1016/j.cell.2015.05.045
Abstract

Lipids play central roles in physiology and disease, where their structural, metabolic, and signaling functions often arise from interactions with proteins. Here, we describe a set of lipid-based chemical proteomic probes and their global interaction map in mammalian cells. These interactions involve hundreds of proteins from diverse functional classes and frequently occur at sites of drug action. We determine the target profiles for several drugs across the lipid-interaction proteome, revealing that its ligandable content extends far beyond traditionally defined categories of druggable proteins. In further support of this finding, we describe a selective ligand for the lipid-binding protein nucleobindin-1 (NUCB1) and show that this compound perturbs the hydrolytic and oxidative metabolism of endocannabinoids in cells. The described chemical proteomic platform thus provides an integrated path to both discover and pharmacologically characterize a wide range of proteins that participate in lipid pathways in cells.

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