Affordable Access

Publisher Website

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

Authors
Type
Published Article
Journal
Biochemistry
0006-2960
Publisher
American Chemical Society
Publication Date
Volume
47
Issue
14
Pages
4211–4220
Identifiers
DOI: 10.1021/bi702319k
PMID: 18341295
Source
Medline

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.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments
F