ADP-ribosylation factor-like 10B (ARL10B) is a member of the ARF GTPase family currently with unknown function. The structure of a truncated mutant of ARL10B (ARL10B-N17) that lacks the N-terminal 17 amino acids has been solved at 1.7Ã… resolution.
The structures of ARF family members in GDP and GTP conformations have suggested that the GDP-GTP exchange induces global conformational changes for effecter recognition and membrane binding; thus the bound nucleotide at the active site determines the differences of ARF proteins between the GDP and the GTP conformations. However, the ARL10B-N17 structure resembles the ARF structures in the GTP conformation although it is still bound to GDP.
This finding suggests that the N-terminal truncation, which mimics the interactions of the N-terminal helix with phospholipid membrane, triggers the conformational switch of ARL10B from the GDP conformation to the GTP conformation. Therefore, the GDP-GTP conformational switch of ARL10B occurs by the N-terminal helix interactions with phospholipid membrane rather than by the GDP-GTP nucleotide exchange at the active site.
Although guanine nucleotide exchange factors (GEFs) of ARL10B are unknown, other ARF GEFs stimulate GDP dissociation with an invariant glutamate. The ARF1-GEF structures have suggested that the GDP conformation of ARF1 is recognized by the GEF. On the basis of the structure of GDP-bound ARL10B-N17, which is similar to the GTP conformation; however, we hypothesize GEF recognition mechanism of ARL10B whereby membrane-recruited ARL10B-GDP adapts a GTP conformation before forming a complex with GEF. Consequently, GDP is dissociated from the ARL10B-GEF complex.
