title: CapZ-lipid membrane interactions: a computer analysis.
abstract: BACKGROUND
  CapZ is a calcium-insensitive and lipid-dependent actin filament capping protein, the main function of which is to regulate the assembly of the actin cytoskeleton. CapZ is associated with membranes in cells and it is generally assumed that this interaction is mediated by polyphosphoinositides (PPI) particularly PIP2, which has been characterized in vitro.
  
  
  RESULTS
  We propose that non-PPI lipids also bind CapZ. Data from computer-aided sequence and structure analyses further suggest that CapZ could become partially buried in the lipid bilayer probably under mildly acidic conditions, in a manner that is not only dependent on the presence of PPIs. We show that lipid binding could involve a number of sites that are spread throughout the CapZ molecule i.e., alpha- and beta-subunits. However, a beta-subunit segment between residues 134-151 is most likely to be involved in interacting with and inserting into lipid membrane due to a slighly higher ratio of positively to negatively charged residues and also due to the presence of a small hydrophobic helix.
  
  
  CONCLUSIONS
  CapZ may therefore play an essential role in providing a stable membrane anchor for actin filaments.
authors.affiliation: Friedrich-Alexander-University of Erlangen-Nuremberg Center for Medical Physics and Technology, Biophysics Group Henkestrasse 91, 91052 Erlangen, Germany. jsmith@biomed.uni-erlangen.de
authors.forename: James
authors.initials: J
authors.lastname: Smith
authors.forename: Gerold
authors.initials: G
authors.lastname: Diez
authors.forename: Anna H
authors.initials: AH
authors.lastname: Klemm
authors.forename: Vitali
authors.initials: V
authors.lastname: Schewkunow
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Goldmann
mesh_terms: D000199:Actins / Q000378:metabolism; D000465:Algorithms; D051347:CapZ Actin Capping Protein / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D003599:Cytoskeleton; D008563:Membrane Lipids / Q000378:metabolism*; D008956:Models, Chemical; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000199:Actins; D051347:CapZ Actin Capping Protein; D008563:Membrane Lipids