Surveying non-visual arrestins reveals allosteric interactions between
functional sites
Abstract
Arrestins are important scaffolding proteins that are expressed in all
vertebrate animals. They regulate cell signaling events upon binding to
active G-protein coupled receptors ( GPCR) and trigger
endocytosis of active GPCRs. While many of the functional sites on
arrestins have been characterized, the question of how these sites
interact is unanswered. We used anisotropic network modelling (
ANM) together with our covariance compliment techniques to
survey all of the available structures of the non-visual arrestins to
map how structural changes and protein-binding affect their structural
dynamics. We found that activation and clathrin binding have a marked
effect on arrestin dynamics, and that these dynamics changes are
localized to a small number of distant functional sites. These sites
include α-helix 1, the lariat loop, nuclear localization domain, and the
C-domain β-sheets on the C-loop side. Our techniques suggest that
clathrin binding and/or GPCR activation of arrestin perturb the dynamics
of these sites independent of structural changes.