The Ras dimer structure

Abstract

By combining the incorporation of unnatural amino acids, click chemistry, FRET and EPR distance measurements, protein modeling and biomolecular simulations, we obtained an unambiguous Ras dimer structural model and disrupt the dimer by mutagenesis.

RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains

“…Specifically, the most prevalent residue contact between the GDP-bound NRAS monomers was a salt bridge between D154 and R161 located on α5 (Rudack et al, 2021). Another prominent contact between the two NRAS monomers was between H131 of α4 helix and E49 of the β2-β3 loop (Rudack et al, 2021). These findings underscore the important role of helices α4 and α5 in stabilizing homodimers of RAS anchored to membranes.…”

“…The presence of the RAS-binding domain of RAF further stabilized dimerization of KRAS4B on membrane. Combining FRET/electron paramagnetic resonance spectroscopy and MD simulations, a recent study also characterized helices α4 and α5 as an important dimer interface in NRAS (Rudack et al, 2021). Specifically, the most prevalent residue contact between the GDP-bound NRAS monomers was a salt bridge between D154 and R161 located on α5 (Rudack et al, 2021).…”

“…Combining FRET/electron paramagnetic resonance spectroscopy and MD simulations, a recent study also characterized helices α4 and α5 as an important dimer interface in NRAS (Rudack et al, 2021). Specifically, the most prevalent residue contact between the GDP-bound NRAS monomers was a salt bridge between D154 and R161 located on α5 (Rudack et al, 2021). Another prominent contact between the two NRAS monomers was between H131 of α4 helix and E49 of the β2-β3 loop (Rudack et al, 2021).…”

RAS Dimers: The Novice Couple at the RAS-ERK Pathway Ball

“…Even though most of the pertinent structural studies have suggested that all RAS isoforms form dimers [43,[45][46][47]49], the detailed molecular structure of RAS dimers has been a matter of conflict. As recently reported by the Gerwert laboratory, the reported RAS dimer structures can be segregated into three main categories based on the regions involved in the interaction between monomers: (i) helix α4 /α5 dimers, (ii) helix α3/α4 dimers, and (iii) β-sheet interaction dimers [52]. In addition, a few studies [47,53] offered enough information on the atomic resolution to provide an accurate molecular description of the dimerization interface and dimer orientation.…”

“…They attached a palmitoyl and a farnesyl group to cysteine 181 via a maleimide group and mixed the lipidated NRAS with 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC) liposomes. In order to give more precise distance measurements between the two NRAS molecules, three different labeling positions were used: S106, T124, and the nucleotide binding site [52]. They demonstrated that the most likely NRAS dimer model corresponded to category I, where the dimer interface involved a helix α4 and helix α5 interaction (Figure 2).…”