A second feature of the
A second feature of the Ras-type GTPases is that their ‘on’ and ‘off’ states are temporally and often spatially separated from one another. This feature is essential for GTPases mediating signaling and other processes that need to be kept ‘off’ until the arrival of signaling cues. The need to recruit extrinsic GEFs and GAPs – which involve transduction of environmental signals, negative or positive feedback control, or translocation of proteins to a different cellular compartment  – further imposes this tight regulation. By contrast, the processes mediated by the SIMIBI family of GTPases and ATPases are often constitutive and must occur rapidly. For example, co-translational protein targeting must occur before the nascent polypeptide reaches a critical length, which imposes a time window of 3–6 s for SRP and SR to complete each targeting Neuregulin/Heregulin-1β (NRG-1β/HRG-1β), human recombinant protein 71, 72. The ability of SRP–SR and Get3 to directly respond to effector molecules in their respective pathways without the need to recruit extrinsic regulatory factors may be especially beneficial for vectorial processes that must occur efficiently.
Concluding Remarks In conclusion, multiple members of the SIMIBI family GTPases and related ATPases couple nucleotide-dependent dimerization to their biological function. Recent work on the SRP–SR and Get3 systems suggests that these proteins can use the conformational plasticity at their dimer interface to directly communicate with upstream and downstream effectors, thus providing spatiotemporal control of complex cellular pathways. More work is needed to decipher the molecular mechanisms of this family of nucleotide hydrolases and understand the chemical and biological logic for utilizing this class of regulatory GTPases (see Outstanding Questions).