Invited review: Mechanisms of GTP hydrolysis and conformational transitions in the dynamin superfamily

Abstract

Dynamin superfamily proteins are multidomain mechano‐chemical GTPases which are implicated in nucleotide‐dependent membrane remodeling events. A prominent feature of these proteins is their assembly‐ stimulated mechanism of GTP hydrolysis. The molecular basis for this reaction has been initially clarified for the dynamin‐related guanylate binding protein 1 (GBP1) and involves the transient dimerization of the GTPase domains in a parallel head‐to‐head fashion. A catalytic arginine finger from the phosphate binding (P‐) loop is repositioned toward the nucleotide of the same molecule to stabilize the transition state of GTP hydrolysis. Dynamin uses a related dimerization‐dependent mechanism, but instead of the catalytic arginine, a monovalent cation is involved in catalysis. Still another variation of the GTP hydrolysis mechanism has been revealed for the dynamin‐like Irga6 which bears a glycine at the corresponding position in the P‐loop. Here, we highlight conserved and divergent features of GTP hydrolysis in dynamin superfamily proteins and show how nucleotide binding and hydrolysis are converted into mechano‐chemical movements. We also describe models how the energy of GTP hydrolysis can be harnessed for diverse membrane remodeling events, such as membrane fission or fusion. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 580–593, 2016.

Structure of a SMG8–SMG9 complex identifies a G-domain heterodimer in the NMD effector proteins

“…S1; Daumke and Praefcke 2016), with the two G domains converging at the loops that are known to harbor the nucleotide-binding motifs (G motifs) in canonical GTPases. However, SMG8 lacks the characteristic residues of G motifs.…”

Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1

“…4). A number of DLPs are involved in the fusion events within the cell (4,10,51). The molecular mechanism of membrane tethering and fusion by dynamin-related GTPases is best understood for atlastins (31,52).…”

“…The latter is subdivided in the middle domain and the C-terminal α12/13 domain (2,10,11). Patches of negatively and positively charged side chains on the LG and α12/13 domains, respectively, are responsible for a tight intramolecular interaction between these domains (12).…”

“…Most members of the dynamin superfamily are involved in processes of membrane reorganization, such as tubulation, fission, and fusion (10). The remodeling of the membrane requires close contact between the protein and the lipid bilayer.…”

Structural insights into the activation mechanism of dynamin-like EHD ATPases

“…In this way, the EH domains were suggested to block a highly conserved second assembly site in the GTPase domain, which extends across the nucleotide binding site. GTPase domain assembly via this "G interface" is a conserved feature in the dynamin superfamily and is often accompanied by activation of the GTPase activity (19).…”