Crystal structure of Leishmania major ADP-ribosylation factor-like 1 and a classification of related GTPase family members in this Kinetoplastid

ADP-ribosylation factor-like (ARL) proteins are small GTPases that undergo conformational changes upon nucleotide binding, and which regulate the affinity of ARLs for binding other proteins, lipids or membranes. There is a paucity of structural data on this family of proteins in the Kinetoplastida, despite studies implicating them in key events related to vesicular transport and regulation of microtubule-dependent processes. The crystal structure of Leishmania major ARL1 in complex with GDP has been determined to 2.1 Å resolution and reveals a high degree of structural conservation with human ADP-ribosylation factor 1 (ARF1). Putative L. major and Trypanosoma brucei ARF/ARL family members have been classified based on structural considerations, amino acid sequence conservation combined with functional data on Kinetoplastid and human orthologues. This classification may guide future studies designed to elucidate the function of specific family members.

. The crystal structure of a Leishmania major ADP-ribosylation-like factor has been determined and in conjunction with sequence comparisons supports an initial classification of small GTPase family members in this Kinetoplastid and the related Trypanosoma brucei.97Research highlights▶ First crystal structure of a Kinetoplastid ADP-ribosylation factor-like protein. ▶ Structure-sequence comparisons of ARF/ARL family from L. major and T. brucei. ▶ Classification of ARF/ARL family including, where available, functional data. ▶ The classification provides a model to guide functional studies.