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Introduction

Figure 1: AMYR

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Amylin Peptide

Structure

The is a heterodimeric protein containing a calcitonin receptor domain, as well as one of three receptor activity modifying proteins(RAMP 1,2, or 3). During feeding, cells in the body will secrete the ligand, amylin. Amylin is a 37 amino acid glucoregulatory hormone that is produced within beta cells of the pancreas. When there is an influx of nutrients in the gastrointestinal tract, the ligand will bind to the heterodimeric receptor, activating the receptor and triggering the corresponding signaling cascade. The overall effect of this cascade is increased satiety, delayed gastric emptying, and inhibition of glucagon secretion. The amylin receptors are widely distributed throughout the central nervous system.

Transmembrane Domain

Within the transmembrane domain of the CTR, hydrophobic R groups span the phospholipid bilayer, anchoring the protein into the cell membrane upon amylin binding to the receptor.

N Terminal Disulfide

Receptor Activity Modifying Proteins

is a key interaction that stabilizes the protein complex and positions the receptor to favorably bind to amylin. The RAMP-CTR interface extends into the plasma membrane, providing additional non-covalent bonding between the protein complex and the cell membrane.

Extracellular Domain - RAMP interactions

The extracellular domain of the CTR primarily contains polar residues in the extracellular space. In order to orient these residues in such a way to facilitate amylin binding, RAMP makes hydrogen bonds with the CTR to increase the rigidity of the receptor binding site.

Bypass Motif

G-alpha Interactions with CTR TMD

In order to transduce the signal across the cell membrane, the binding of amylin will induce a conformational change that allows for the CTR to make favorable interactions with the G alpha subunit. Two interactions shown and activate the G-protein and propel downstream signaling.

Function

Relevance