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ARF4 - Human ADP-ribosylation Factor 4
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 2.7Å. 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.