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ARL5 - Human ADP-ribosylation Factor-like 5

PDB entry: 1Z6Y

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ADP-ribosylation factor-like 5 (ARL5) belongs to the ARF family of GTP-binding proteins. The cellular function of ARL5 is currently unknown. The primary sequence of ARL5 is most similar to that of ADP-ribosylation factor-like 8 (ARL8), which is potentially involved in brain development.

Here, we solved the structure of the complex of ARL5 with GDP. The ARL5-GDP structure is similar to our recent ARL8-GDP structure (PDB code 1YZG) as expected from their sequence similarity. Particularly the N-terminal helix forms hydrophobic interactions with the main body of ARL5. This N-terminal helix binding site of ARL5 is located opposite from the GTP/GDP binding site. Based on the membrane recruitment mechanism of the ARF family proteins, the N-terminal helix will be displaced to interact with membranes when GTP replaces GDP.

Although the ARL5-GTP structure is not known, we hypothesize that the hydrophobic side chains of the N-terminal helix of ARL5 will be responsible for the interactions with membranes. Further studies will be necessary to prove this hypothesis.

Materials and Methods