The small GTPases Ras and Rheb studied by multidimensional NMR spectroscopy: Structure and function

Miriam Schöpel, Veena Nambiar Potheraveedu, Thuraya Al-Harthy, Raid Abdel-Jalil, Rolf Heumann, Raphael Stoll

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Ras GTPases are key players in cellular signalling because they act as binary switches. These states manifest through toggling between an active (GTP-loaded) and an inactive (GDP-loaded) form. The hydrolysis and replenishing of GTP is controlled by two additional protein classes: GAP (GTPase-activating)- and GEF (Guanine nucleotide exchange factors)-proteins. The complex interplay of the proteins is known as the GTPase-cycle. Several point mutations of the Ras protein deregulate this cycle. Mutations in Ras are associated with up to one-third of human cancers. The three isoforms of Ras (H, N, K) exhibit high sequence similarity and mainly differ in a region called HVR (hypervariable region). The HVR governs the differential action and cellular distribution of the three isoforms. Rheb is a Ras-like GTPase that is conserved from yeast to mammals. Rheb is mainly involved in activation of cell growth through stimulation of mTORC1 activity. In this review, we summarise multidimensional NMR studies on Rheb and Ras carried out to characterise their structure-function relationship and explain how the activity of these small GTPases can be modulated by low molecular weight compounds. These might help to design GTPase-selective antagonists for treatment of cancer and brain disease.

Original languageEnglish
Pages (from-to)577-588
Number of pages12
JournalBiological Chemistry
Volume398
Issue number5-6
DOIs
Publication statusPublished - May 1 2017

    Fingerprint

Keywords

  • ligand binding
  • nuclear magnetic resonance (NMR)
  • Ras
  • Rheb

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Cite this