7tyn

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Calcitonin Receptor in complex with Gs and salmon calcitonin peptide

Structural highlights

7tyn is a 6 chain structure with sequence from Homo sapiens, Lama glama and Salmo salar. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.6Å
Ligands:NAG, NH2, P42, PLM, Y01
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B5XGR7_SALSA Causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.[ARBA:ARBA00003306]

Publication Abstract from PubMed

Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMY(1)R, AMY(2)R, and AMY(3)R. Selective AMYR agonists and dual AMYR/CTR agonists are being developed as obesity treatments; however, the molecular basis for peptide binding and selectivity is unknown. We determined the structure and dynamics of active AMYRs with amylin, AMY(1)R with salmon CT (sCT), AMY(2)R with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. The conformation of amylin-bound complexes was similar for all AMYRs, constrained by the RAMP, and an ordered midpeptide motif that we call the bypass motif. The CT-bound AMYR complexes were distinct, overlapping the CT-bound CTR complexes. Our findings indicate that activation of AMYRs by CT-based peptides is distinct from their activation by amylin-based peptides. This has important implications for the development of AMYR therapeutics.

A structural basis for amylin receptor phenotype.,Cao J, Belousoff MJ, Liang YL, Johnson RM, Josephs TM, Fletcher MM, Christopoulos A, Hay DL, Danev R, Wootten D, Sexton PM Science. 2022 Mar 25;375(6587):eabm9609. doi: 10.1126/science.abm9609. Epub 2022 , Mar 25. PMID:35324283[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. 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

Contents


PDB ID 7tyn

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