Morin-Leisk et al. describe how a salt bridge drives a conformational change in the atlastin GTPase to promote membrane fusion and ER branching.
Atlastins are membrane-anchored members of the dynamin family of GTPases that tether and fuse ER tubules together in order to maintain the organelle's branched morphology. Crystal structures suggest that atlastin molecules in opposing ER membranes initially dimerize head-on to tether the membranes together. GTP hydrolysis is then thought to trigger a rotation in the dimer's conformation that brings the two membranes close enough to fuse with each other.
Morin-Leisk et al. identified several mutations in atlastin that prevented the GTPase from maintaining a branched ER network. Two of these mutations affected either the glutamate or the lysine residue of an ionic salt bridge that forms when atlastin assumes its “postfusion” conformation. Altering the charge on either of these polar amino acids had no effect on GTP binding or hydrolysis but inhibited the assembly of “postfusion” atlastin dimers. Restoring the salt bridge by reversing the charge on both residues rescued atlastin dimerization and ER branching.
The salt bridge therefore promotes ER tubule fusion by stabilizing atlastin's postfusion conformation. Surprisingly, Morin-Leisk et al. found that GTP hydrolysis wasn't required for the transition to this conformation, at least for soluble versions of atlastin lacking the GTPase's transmembrane domain. Senior author Tina Lee now wants to determine whether the same is true for full-length atlastin and, if so, to investigate which part of atlastin's fusion mechanism is dependent on nucleotide hydrolysis.