PROSITE documentation PDOC51719

Septin-type guanine nucleotide-binding (G) domain profile

The P-loop (see <PDOC00017>) guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

Septins are a family of eukaryotic cytoskeletal proteins conserved from yeasts to humans. The septin family belongs to the guanosine-triphosphate (GTP)ase superclass of P-loop nucleoside triphosphate (NTP)ases. Septins participate in diverse cellular functions including cytokinesis, vesicle trafficking, vesicle fusion, axonal guidance and migration, diffusion barrier, scaffolds, pathogenesis and others. Septin monomers form homo- and hetero-oligomeric complexes that assemble into filaments. Structurally all septins have a GTP-binding domain flanked by N- and C-terminal regions of variable length. The GTP-binding domain is the most highly conserved and is characterized by the presence of three of the five classical GTP-binding motifs. The G1 motif (or Walker A box, GxxxxGKS/T) forms the P-loop, which interacts directly with the nucleotide, whereas the G3 (DxxG) and G4 (xKxD) motifs are respectively essential for Mg(2+) binding and for conferring GTP binding specificity over other nucleotides. The basic structure of the septin-type G domain closely resembles the canonical G domain exemplified by Ras, with six β-strands and five α-helices. A unique feature of the septin-type G domain is the presence of four additional elements compared to Ras (see <PDB:2QA5>). These are the helix α5' between α4 and β6, the two antiparallel strands β7 and β8, and the α6 C-terminal helix that points away from the G domain at a 90 degrees angle relative to the axis of interaction between subunits [1,2,3,4,5].

The profile we developed covers the entire septin-type G domain.