Attachment of rod-like (BAR) proteins and membrane shape.

D Kabaso,A Iglic,J Gimsa,V Kralj-Iglic,P Elter,E Gongadze,U Van Rienen,A Iglič,V Kralj-Iglič

doi:10.2174/138955711795305353

Abstract

Previous studies have shown that cellular function depends on rod-like membrane proteins, among them Bin/Amphiphysin/Rvs (BAR) proteins may curve the membrane leading to physiologically important membrane invaginations and membrane protrusions. The membrane shaping induced by BAR proteins has a major role in various biological processes such as cell motility and cell growth. Different models of binding of BAR domains to the lipid bilayer are described. The binding includes hydrophobic insertion loops and electrostatic interactions between basic amino acids at the concave region of the BAR domain and negatively charged lipids. To shed light on the elusive binding dynamics, a novel experiment is proposed to expand the technique of single-molecule AFM for the traction of binding energy of a single BAR domain.

Highlights

The membrane curvature induced by BAR proteins has a major role in various biological processes such as cell shaping, cell growth, cell motility, receptor-ligand interactions, adhesion to the extracellular matrix, and intracellular signalling [1,2,3,4,5,6,7]
The gene encoding one of the BAR proteins in humans has been shown to be fused to mixed lineage leukaemia (MLL) observed in patients suffering from acute myelogenous leukaemia [8]
We propose that the dynamics of a BAR domain binding to a lipid bilayer may include three steps: a) the two tips of a BAR domain are attracted to the membrane by strong electrostatic interactions towards negatively charged lipids (Fig. 2a); b) the two hydrophobic loops are inserted into the hydrophobic layer of the inner leaflet (Fig. 2b)

Summary

INTRODUCTION

The membrane curvature induced by BAR proteins has a major role in various biological processes such as cell shaping, cell growth, cell motility, receptor-ligand interactions, adhesion to the extracellular matrix, and intracellular signalling [1,2,3,4,5,6,7]. BAR domains are rod-like membrane proteins which can sense or induce a curvature to the membrane [13,14,15]. By mapping their X-ray crystallography structures, it is evident that BAR domains are homodimers of crescent-like shapes that are rich with basic amino-acids at the concave side [13,16,17,18] (Fig. 1). The case of rigid (stiff) rod-like proteins is discussed, where the effects of BAR domain orientations are taken into account. In the discussion section, we propose an experiment by which it may be possible to measure the binding energy of a BAR domain to a lipid bilayer/cell membrane, as well as possible applications of the outlined experiments and theory

A MODEL FOR THE BINDING OF BAR DOMAINS

DISCUSSION