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

Structure. 2017 Jul 5;25(7):997-1010.e4. doi: 10.1016/j.str.2017.05.007. Epub 2017 Jun 9.


The endoplasmic reticulum (ER) forms a branched, dynamic membrane tubule network that is vital for cellular function. Branching arises from membrane fusion facilitated by the GTPase atlastin (ATL). Many metazoan genomes encode for three ATL isoforms that appear to fulfill partially redundant function despite differences in their intrinsic GTPase activity and localization within the ER; however, the underlying mechanistic differences between the isoforms are poorly understood. Here, we identify discrete temporal steps in the catalytic cycle for the two most dissimilar isoforms, ATL1 and ATL3, revealing an overall conserved progression of molecular events from nucleotide binding and hydrolysis to ATL dimerization and phosphate release. A crystal structure of ATL3 suggests a mechanism for the displacement of the catalytic Mg2+ ion following guanosine triphosphate (GTP) hydrolysis. Together, the data extend the mechanistic framework for how GTP hydrolysis drives conformational changes in ATL and how the cycle is reset for subsequent rounds of catalysis.

Keywords: GTPase; dynamin-related proteins; enzyme mechanism; membrane fusion; nucleotide exchange.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Magnesium / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Protein Binding


  • Membrane Proteins
  • Guanosine Triphosphate
  • ATL1 protein, human
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • ATL3 protein, human
  • Magnesium