GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins

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Abstract

Cell biology depends on the interactions of macromolecules, such as protein—DNA, protein—protein or protein—nucleotide interactions. GTP-binding proteins are no exception to the rule. They regulate cellular processes as diverse as protein biosynthesis and intracellular membrane trafficking. Recently, a large number of genes encoding GTP-binding proteins and the proteins that interact witht these molecular switches have been cloned and expressed. The 3D structures of some of these have also been elucidated

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      Membrane attachment can also be regulated by ubiquitination (Baietti et al., 2016; Steklov et al., 2018; Thurman et al., 2020), phosphorylation of the C terminus as well as other post-translational modifications, such as acetylation, and calmodulin (Jang et al., 2017, 2019; Nussinov et al., 2017b). As members of the small GTPase family, Ras proteins function as molecular switches between their two states (Bourne et al., 1991; Cherfils and Zeghouf, 2013; Downward, 1990; Geyer and Wittinghofer, 1997; Grand and Owen, 1991; Lamontanara et al., 2014; Lowy et al., 1991; Sprang, 1997; Takai et al., 2001; Vetter and Wittinghofer, 2001; Wittinghofer and Pai, 1991; Wittinghofer and Vetter, 2011). Inactivation is mediated by GTPase-activating proteins (GAPs) that hydrolyze the GTP to GDP (Wittinghofer et al., 1997).

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