My name is Seva Gurevich, I'm from Vanderbilt University in Nashville, Tennessee.
We will discuss the structure and biological functions of arrestin proteins.
Arrestins were first discovered as proteins that bind
active phosphorylated G protein-coupled receptors (GPCRs for short).
All animals have hundreds of different GPCR sub-types, that respond to a variety of stimuli.
Structurally, GPCR activators range from photons of light, ions,
small molecules, to peptides and to large proteins.
GPCRs activate heterotrimeric G proteins,
that's why they are called G protein-coupled receptors.
Activated G proteins, in their turn, activate a variety of intracellular effects.
Here is the structure of a prototypical GPCR, rhodopsin,
which mostly consists of the conserved GPCR core, that includes
seven transmembrane helices forming a twisted bundle.
The first discovered function of arrestins was
their role in homologous desensitization of GPCRs,
that is, the loss of sensitivity of the activated receptor.
Active receptors sequentially activate many G protein molecules.
The active receptor is phosphorylated by GRKs (GPCR kinases),
arrestins then bind active phosphorylated receptors,
blocking their coupling to G proteins.
Receptor-bound arrestins bind clathrin and clathrin adaptor AP2,
facilitating receptor internalization, and interact with
a variety of effectors initiating certain branches of signaling.