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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Abankwa D, Gorfe AA, Hancock JF
Publiceringsår: 2008
Tidskrift: Cell Cycle
Tidskriftsakronym: CELL CYCLE
Volym: 7
Nummer: 17
Artikelns första sida, sidnummer: 2667
Artikelns sista sida, sidnummer: 2673
Antal sidor: 7
ISSN: 1538-4101


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.


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

Senast uppdaterad 2019-14-12 vid 04:13