GTP-binding protein regulators articles from across Nature Portfolio

Time-resolved cryo-EM is used to capture structural transitions during G-protein activation stimulated by a G-protein-coupled receptor.

Structural and functional studies highlight the molecular regulation of assembling the mitochondrial division machinery. The core unit is closed, and specific interactions open this unit to facilitate assembly at the right place and time in cells.

The HOPS complex mediates membrane tethering and autophagosome-lysosome fusion. Here, the authors biochemically reconstitute the mammalian HOPS in protoliposomes and propose a model of complex assembly that depends on Rab2 and Rab39A.

EPAC1 is a cAMP-activated guanine nucleotide exchange factor (GEF) for Rap GTPases and a major transducer of cAMP signaling. Here, the authors show anionic membranes can activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity.

Traditional approaches to covalent drug design postulate that noncovalent binding affinity (K_i) should be in the nanomolar range for the lead compound to be attractive. A study by Hansen et al. suggests that covalent K-Ras inhibitors can have weak noncovalent binding affinity yet have fast chemical reactivity (k_inact), because K-Ras enhances the covalent reactivity of bound inhibitor, similarly to how enzymes activate their substrates.

Drosophila Skywalker regulates the GTPase Rab35, thereby controlling the turnover of synaptic-vesicle proteins. A new crystal structure of the TBC domain of Skywalker reveals an unexpected phosphoinositide-binding pocket, which is critical for synaptic function and is disrupted in DOORS syndrome–causing mutations in the human Skywalker homolog TBC1D24.