Article (Scientific journals)
Mechanisms of Ras Membrane Organization and Signaling: Ras Rocks Again.
Abankwa, Daniel; Gorfe, Alemayehu A.
2020In Biomolecules, 10 (11)
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Keywords :
HVR; Raf; Ras; Ras orientation; dimerization; membrane; nanocluster; structure
Abstract :
[en] Ras is the most frequently mutated oncogene and recent drug development efforts have spurred significant new research interest. Here we review progress toward understanding how Ras functions in nanoscale, proteo-lipid signaling complexes on the plasma membrane, called nanoclusters. We discuss how G-domain reorientation is plausibly linked to Ras-nanoclustering and -dimerization. We then look at how these mechanistic features could cooperate in the engagement and activation of RAF by Ras. Moreover, we show how this structural information can be integrated with microscopy data that provide nanoscale resolution in cell biological experiments. Synthesizing the available data, we propose to distinguish between two types of Ras nanoclusters, an active, immobile RAF-dependent type and an inactive/neutral membrane anchor-dependent. We conclude that it is possible that Ras reorientation enables dynamic Ras dimerization while the whole Ras/RAF complex transits into an active state. These transient di/oligomer interfaces of Ras may be amenable to pharmacological intervention. We close by highlighting a number of open questions including whether all effectors form active nanoclusters and whether there is an isoform specific composition of Ras nanocluster.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Abankwa, Daniel  ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Gorfe, Alemayehu A.
External co-authors :
yes
Language :
English
Title :
Mechanisms of Ras Membrane Organization and Signaling: Ras Rocks Again.
Publication date :
November 2020
Journal title :
Biomolecules
ISSN :
2218-273X
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Volume :
10
Issue :
11
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 18 January 2021

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