Mechanisms of Ras membrane organization and signaling: Ras on a rocker

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Abankwa D, Gorfe AA, Hancock JF
Publisher: LANDES BIOSCIENCE
Publication year: 2008
Journal: Cell Cycle
Journal acronym: CELL CYCLE
Volume number: 7
Issue number: 17
Start page: 2667
End page: 2673
Number of pages: 7
ISSN: 1538-4101


Abstract

Understanding the signalling function of Ras GTPases has been the focus of much research for over 20 years. Both the catalytic domain and the membrane anchoring C terminal hypervariable region (HVR) of Ras are necessary for its cellular function. However, while the highly conserved catalytic domain has been characterized in atomic detail, the structure of the full-length membrane-bound Ras has remained elusive. Lack of structural knowledge on the full-length protein limited our understanding of Ras signalling. For example, structures of the Ras catalytic domain solved in complex with effectors do not provide a basis for the functional specificity of different Ras isoforms. Recent molecular dynamics simulations in combination with biophysical and cell biological experiments have shown that the HVR and parts of the G domain cofunction with the lipid tails to anchor H-ras to the plasma membrane. In the GTP-bound state, H-ras adopts an orientation that allows read out by Ras effectors and translation into corresponding MAPK signalling. Here we discuss details of an analysis that suggests a novel balance model for Ras functioning. The balance model rationalizes Ras membrane orientation and may help explain isoform specific interactions of Ras with its effectors and modulators.


Keywords

FRET, microdomain, nanocluster, plasma membrane, Ras, structure

Last updated on 2019-18-06 at 05:00