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ARF4 - Human ADP-ribosylation Factor 4

PDB entry: 1Z6X

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ADP-ribosylation factor 4 (ARF4) is a member of the Ras small G protein superfamily. It is involved in membrane trafficking and mediating epidermal growth factor receptor-dependent phospholipase D2 activation. Also, ARF4 interacts with the C-terminal cytoplasmic domain of Rhodopsin. The ARF4-Rhodopsin interactions suggest the role of ARF4 in targeting Rhodopsin to rod outer segments, which is required for normal retinal development. As the C-terminal tetrapeptide mutations in Rhodopsin cause severe autosomal dominant retinitis pigmentosa, understanding the ARF4-Rhodopsin interactions may lead to some ideas for potential therapeutic approaches.

Here we solved the structure of human ARF4 bound to ADP at 2.7. The ARF4-GDP structure illustrates the nucleotide binding site and the specific interactions between ARF4 and GDP.

The ARF4-GDP structure, compared with other known ARF structures, will be a valuable tool in understanding the specificity of Rhodopsin for ARF4.

Materials and Methods