Action of Antimicrobial Peptides


            Huey W. Huang

Department of Physics, Rice University, Houston, Texas, USA 77251-1892


The antimicrobial peptides produced by the innate immune system are a subject of current interest (Science, News Focus, 16 March 2001).  They are not only widely effective but may provide a new source of antibiotics.  I will introduce this subject and set up the problem for biophysical investigations.  Antimicrobial peptides are different from most other proteins in two ways.  First, they target the lipid matrix of plasma membranes.  Second, they function in a highly cooperative fashion.  By the method of oriented circular dichroism, we found that the peptides have two physical states of binding to membranes.  By neutron and X-ray diffraction, we found that the peptides form transmembrane pores in one of the two states.  In the other state, the peptides are bound to the headgroup regions of lipid bilayers, causing a membrane thinning effect.  The mechanism of transition between the two states will be discussed.  The peptide concentration for this transition varies from one cell membrane to another, allowing the cell-type selectivities exhibited by antimicrobial peptides. (Huang, Biochemistry 39, 8347, 2000)