Structural Determinants of Arrestin Functions - Progress in Molecular Biology and Translational Science - page 56

Figure 3.1 Basal conformation of different arrestin subtypes. Superimposition of the
crystal structures of the two monomers in the arrestin-1 tetramer (Arr1A, red and Arr1D,
pink), 18 two monomers of the arrestin-2 dimer (Arr2A, light blue and Arr2B, dark blue), 19
and arrestin-3 (Arr3, yellow) 20 shows remarkably similar cores of both domains and var-
iable structure of the loops and inter-domain hinge. Importantly, the variability of these
elements in different monomers of the same arrestin (compare Arr1A and Arr1D, as well
as Arr2A and Arr2B) is essentially as great as between arrestin subtypes, suggesting that
it reflects the flexibility of these loops, rather than their subtype-specific conformations.
Black and red circles show the location of the two key intramolecular interactions that
hold arrestins in their basal state, the polar core in the inter-domain interface, and the
three-element interaction between -strand XX in the C-tail,

respectively. The panels above show detailed structure of these elements revealing their
extremely high conservation, down to the orientation of the side chains. Right: The polar
core, main phosphate sensor. Left: The three-element interaction. In both panels, resi-
due numbers of bovine proteins are indicated as follows: arrestin-1, red; arrestin-2, blue;
arrestin-3, green.

-strand I, -helix I, and

b a b

3. HOW DO ARRESTINS FIT RECEPTORS?
There is an obvious caveat in fitting known arrestin and receptor
structures: for the complex to form, both arrestin and receptor must be in
an active conformation, and the receptor also must be phosphorylated. 14,30