Membrane Targeting: Methods


The responsiveness of cells to external signals, or cell signalling, involves highly regulated sequences of biochemical reactions at the plasma membrane. When receptor proteins in the outer surface of the plasma membrane are activated by environmental signals, they undergo shape change or chemical modification to assemble internal proteins into an organised complex on the inner surface. Specific protein domains and lipids (fats) that are physically attached to proteins tether key components of this complex to the lipid bilayer of the membrane. Scientists have developed cell‐based and chemical techniques that allow them to introduce specific membrane‐targeting motifs into proteins to produce and study how this may alter cell behaviour. As a result, a great deal has been learned about the molecular basis of membrane targeting by lipid‐modified proteins. This knowledge holds a promise for the rational design of new compounds to prevent defective membrane targeting that could lead to abnormal signalling and the development of diseases.

Key Concepts:

  • Lipid bilayers provide the fundamental architecture of biological membranes.

  • The two‐dimensional surface of membranes provides a structural framework to organise multiple signalling proteins.

  • Proteins target membranes using globular domains and lipids that are covalently attached to them.

  • The most common lipid‐based membrane‐targeting motifs in the interior of the cell include modification of cysteine and glycine amino acids by acyl and prenyl groups.

  • G‐proteins are the quintessential examples of membrane targeting by lipidation.

  • Modern cell biology and chemical biology techniques can be used to artificially attach lipids to proteins.

  • Prevention of defective membrane targeting is being pursued as a new therapeutic strategy.

Keywords: fatty acid modification; lipid bilayer; membrane proteins; protein design; chimaeric protein; chemical biology; computational biology

Figure 1.

A schematic example for the assembly of multiple signalling proteins on the plasma membrane. Activation of the lipid‐modified membrane‐associated Ras proteins (RAS*) triggers the formation of a cluster of multiple proteins of the MAPK module (Raf, MEK and ERK) and scaffold proteins (Galectin and KSR1).



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Gorfe, Alemayehu A, and Hocker, Harrison J(Jan 2012) Membrane Targeting: Methods. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002615.pub2]