Affordable Access

deepdyve-link
Publisher Website

Interactions of the pleckstrin homology domain with phosphatidylinositol phosphate and membranes: characterization via molecular dynamics simulations.

Authors
  • Psachoulia, Emi
  • Sansom, Mark S P
Type
Published Article
Journal
Biochemistry
Publication Date
Apr 08, 2008
Volume
47
Issue
14
Pages
4211–4220
Identifiers
DOI: 10.1021/bi702319k
PMID: 18341295
Source
Medline
License
Unknown

Abstract

The mechanism of interaction of pleckstrin homology (PH) domains with phosphatidylinositol 4,5-bisphosphate (PIP 2)-containing lipid bilayers remains uncertain. While crystallographic studies have emphasized PH-inositol 1,4,5-trisphosphate (IP 3) interactions, biophysical studies indicate a degree of less specific protein-bilayer interactions. We have used molecular dynamics simulations to characterize the interactions of the PH domain from phospholipase C-delta1 with IP 3 and with PIP 2, the latter in lipid bilayers and in detergent micelles. Simulations of the PH domain in water reveal a reduction in protein flexibility when IP 3 is bound. Simulations of the PH domain bound to PIP 2 in lipid bilayers indicate a tightening of ligand-protein interactions relative to the PH-IP 3 complex, alongside formation of H-bonds between PH side chains and lipid (PC) headgroups, and a degree of penetration of hydrophobic side chains into the core of the bilayer. Comparison with simulations of the PH-bound domain to a PC bilayer in the absence of PIP 2 suggests that the presence of PIP 2 increases the extent of PH-membrane interactions. Thus, comparative molecular dynamics simulations reveal how a PI-binding domain undergoes changes in conformational dynamics on binding to a PIP 2-containing membrane and how interactions additional to those with the PI headgroup are formed.

Report this publication

Statistics

Seen <100 times