Crystal Structure of p44, a Constitutively Active Splice Variant of Visual Arrestin

Visual arrestin specifically binds to photoactivated and phosphorylated rhodopsin and inactivates phototransduction. In contrast, the p44 splice variant can terminate phototransduction by binding to nonphosphorylated light-activated rhodopsin. Here we report the crystal structure of bovine p44 at a resolution of 1.85 Å. Compared to native arrestin, the p44 structure reveals significant differences in regions crucial for receptor binding, namely flexible loop V–VI and polar core regions. Additionally, electrostatic potential is remarkably positive on the N-domain and the C-domain. The p44 structure represents an active conformation that serves as a model to explain the ‘constitutive activity’ found in arrestin variants.

Graphical AbstractFigure optionsDownload high-quality image (101 K)Download as PowerPoint slideHighlights
► The crystal structure of the arrestin splice variant p44 was determined at a resolution of 1.85 Å.
► Structural differences in flexible loop V–VI and polar core regions are highlighted.
► The electrostatic potential is remarkably positive on the N-domain and the C-domain in p44.
► The p44 structure provides the first direct structural evidence supporting the role of C-tail in the arrestin activation mechanism.
► The p44 structure represents an active conformation..