Standard Article

Membrane Targeting: Methods

  1. Alemayehu A Gorfe,
  2. Harrison J Hocker

Published Online: 15 JAN 2012

DOI: 10.1002/9780470015902.a0002615.pub2

eLS

eLS

How to Cite

Gorfe, A. A. and Hocker, H. J. 2012. Membrane Targeting: Methods. eLS. .

Author Information

  1. University of Texas Health Science Center, Houston, Texas, USA

Publication History

  1. Published Online: 15 JAN 2012

Abstract

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