Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion

Abstract

The crystal structures of the N-terminal cytosolic domain of Sey1p shed light on the mechanism of Sey1p-mediated ER membrane fusion.

Timing and Reset Mechanism of GTP Hydrolysis-Driven Conformational Changes of Atlastin

“…The hATL3 structure revealed a novel active site organization: whereas hATL1 (PDB 3Q5E), dmATL (PDB 3X1D), and Sey1 (PDB 5CA8) exhibit the same binding configuration for GDP•Mg 2+ (Byrnes and Sondermann, 2011; Wu et al, 2015; Yan et al, 2015), the canonical Mg 2+ was displaced by the guanidinium group of an intramolecular arginine residue at position 109 (R 109 ) in the hATL3 structure (Figures 6C and 6D), an active site residue that is distinct from the catalytic arginine finger (R 70 in hATL3, R 77 in hATL1). The conformation of R 109 is further stabilized through a salt-bridge formed with an aspartate residue at position 142, one of the main Mg 2+ -coordinating residues in ATLs (Figure 6C) (Bian et al, 2011; Byrnes and Sondermann, 2011).…”

“…ATLs are resident to the tubular ER, where they catalyze membrane fusion to maintain ER morphology; proper control of this process is essential for axonal development, integrity, and signaling (Hu et al, 2009; Muriel et al, 2009; Orso et al, 2009; Rao et al, 2016; Renvoisé and Blackstone, 2010; Rismanchi et al, 2008; Yan et al, 2015; Li et al, 2017). Whereas hATL1 and hATL2 appear to be distributed throughout the tubular ER, hATL3 has a tendency to form puncta at tubule three-way junctions (Wang et al, 2016; Yan et al, 2015). hATL1 and hATL3 also localize to peripheral ER sheets and large sheet-like three-way junctions, and recently, super resolution microscopy techniques revealed that these structures are areas of dense tubular matrices (Nixon-Abell et al, 2016).…”

“…Functional redundancy has been shown for hATL1 and hATL2 due to their ability to restore a branched ER morphology when expressed in COS-7 cells devoid of all ATLs. However, hATL3 fails to fully rescue the branched ER phenotype suggesting that not all isoforms are mechanistically equivalent (Hu et al, 2015; Yan et al, 2015). Isoform differences have been shown biochemically through phosphate release kinetics, where hATL1 and hATL3 have the highest and lowest catalytic rates (Hu et al, 2015).…”

Shaping the Endoplasmic Reticulum into a Social Network

“…Structural studies of human ATL1 and Candida albicans Sey1p have provided significant insight into the mechanism by which these GTPases fuse membranes [30][31][32][33]. ATL and Sey1p/RHD3 contain an N-terminal GTPase and a helical bundle domain, followed by a TMH and C-terminal tail (CT).…”

Advances in Plant ER Architecture and Dynamics

“…At a subcellular level, the loss of RHD3 also reduces the formation of three-way junctions owing to the capacity of the protein to fuse membranes in a GTP-dependent fashion (Ueda et al, 2016). In this context, RHD3 functions analogously to similar membrane-associated dynamin-like GTPases, such as metazoan atlastin and yeast Sey1p Zhang et al, 2013;Yan et al, 2015). Nonetheless, it has been shown that the functional regulation of RHD3 may depend on plant-unique features.…”