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 <scene name='10/1038828/Ctr_g_alpha/14'>here </scene> and <scene name='10/1038828/Ctr_g_alpha/12'>here </scene> activate the G-protein and propel downstream signaling.
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 <scene name='10/1038828/Ctr_g_alpha/15'>here </scene> and <scene name='10/1038828/Ctr_g_alpha/12'>here </scene> activate the G-protein and propel downstream signaling.
The amylin g-protein coupled receptor 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
RAMP CTR Interface 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. RAMP CTR Extracellular Domain Interaction
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 here and here activate the G-protein and propel downstream signaling.
Function
Relevance
↑Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:https://dx.doi.org/10.1002/ijch.201300024
↑Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
↑Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:https://dx.doi.org/10.1002/1873-3468.12677
↑Cao J, Belousoff MJ, Liang YL, Johnson RM, Josephs TM, Fletcher MM, Christopoulos A, Hay DL, Danev R, Wootten D, Sexton PM. A structural basis for amylin receptor phenotype. Science. 2022 Mar 25;375(6587):eabm9609. PMID:35324283 doi:10.1126/science.abm9609
References
Student Contributors
Ben Whiteside,
Mathias Vander Eide,
Andrew Helmerich,
