Format

Send to

Choose Destination
Biophys J. 2004 Apr;86(4):1969-86.

A computational model for the electrostatic sequestration of PI(4,5)P2 by membrane-adsorbed basic peptides.

Author information

1
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.

Abstract

The multivalent acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) plays a key role in many biological processes. Recent studies show that unstructured clusters of basic residues from a number of peripheral proteins can laterally sequester PI(4,5)P2 in membranes. Specifically, experiments suggest that the basic effector domain of the myristoylated alanine-rich C kinase substrate (MARCKS), or a peptide corresponding to this domain, MARCKS(151-175), sequesters several PI(4,5)P2 and that this sequestration is due to nonspecific electrostatic interactions. Here, we use the finite difference Poisson-Boltzmann method to test this hypothesis by calculating the electrostatic free energy of lateral sequestration of PI(4,5)P2 by membrane-adsorbed basic peptides: Lys-7, Lys-13, and FA-MARCKS(151-175), a peptide based on MARCKS(151-175). In agreement with experiments, we find that the electrostatic free energy becomes more favorable when: 1), Lys-13 and FA-MARCKS(151-175) sequester several PI(4,5)P2; 2), the linear charge density of the basic peptide increases; 3), the mol percent monovalent acidic lipid in the membrane decreases; and 4), the ionic strength of the solution decreases. In addition, the electrostatic sequestration free energy is in excess of the entropic penalty associated with localizing PI(4,5)P2. Our calculations, thus, provide a structural and quantitative description of the observed interaction of PI(4,5)P2 with membrane-adsorbed basic sequences.

PMID:
15041641
PMCID:
PMC1304052
DOI:
10.1016/S0006-3495(04)74260-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center