The Ras G Domain Lacks the Intrinsic Propensity to Form Dimers

Biophysical Journal
Elizaveta A KovriginaEvgenii L Kovrigin

Abstract

Ras GTPase is a molecular switch controlling a number of cellular pathways including growth, proliferation, differentiation, and apoptosis. Recent reports indicated that Ras undergoes dimerization at the membrane surface through protein-protein interactions. If firmly established this property of Ras would require profound reassessment of a large amount of published data and modification of the Ras signaling paradigm. One proposed mechanism of dimerization involves formation of salt bridges between the two GTPase domains (G domains) leading to formation of a compact dimer as observed in Ras crystal structures. In this work, we interrogated the intrinsic ability of Ras to self-associate in solution by creating conditions of high local concentration through irreversibly tethering the two G domains together at their unstructured C-terminal tails. We evaluated possible self-association in this inverted tandem conjugate via analysis of the time-domain fluorescence anisotropy and NMR chemical shift perturbations. We did not observe the increased rotational correlation time expected for the G domain dimer. Variation of the ionic strength (to modulate stability of the salt bridges) did not affect the rotational correlation time in the ...Continue Reading

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Citations

Dec 29, 2015·Current Opinion in Structural Biology·Avik BanerjeeVadim Gaponenko
Jan 27, 2016·Journal of the American Chemical Society·Jean K ChungJay T Groves
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Jul 2, 2021·Chemical Science·Till RudackCarsten Kötting
Aug 14, 2021·Biophysical Journal·Frank HeinrichMathias Lösche

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