8AX6: CGRP receptor ectodomain heterodimer

Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0029882. Determined by X-ray diffraction at 1.9 Å resolution. Released 7 Dec 2022.

Method: X-ray diffraction
Resolution: 1.9 Å
Organisms: Escherichia coli K-12, Homo sapiens
Chains: 1
Atoms: 5,127
Mol. weight: 67.45 kDa
Ligands: OP9
Released: 7 Dec 2022

Explore 8AX6 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8AX6 contains 37 α-helices and 35 β-strands across 1 chain. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 37 helices, 35 β-strands

Element	Residues	Length	Sheet
β-strand	8-12	5	1
α-helix	19-33	15
β-strand	36-40	5	1
α-helix	45-54	10
β-strand	61-65	5	1
α-helix	66-68	3
α-helix	69-74	6
β-strand	78	1	2
α-helix	79-81	3
α-helix	85-88	4
β-strand	91	1	3
α-helix	93-98	6
β-strand	100-101	2	4
β-strand	104-105	2	4
β-strand	108-113	6	1
β-strand	116-120	5	5
β-strand	130	1	6
α-helix	131-133	3
α-helix	134-142	9
β-strand	147-149	3	5
α-helix	156-165	10
β-strand	169-174	6	7
β-strand	177-184	8	7
α-helix	188-202	15
α-helix	212-220	9
β-strand	224-229	6	5
α-helix	231-233	3
α-helix	234-240	7
β-strand	244-247	4	5
α-helix	248-250	3
β-strand	251-252	2	6
β-strand	255-256	2	6
α-helix	257	1
α-helix	259	1
β-strand	260-261	2	8
β-strand	262-268	7	1
β-strand	269	1	2
α-helix	275-281	7
α-helix	282-286	5
α-helix	289-298	10
β-strand	303-304	2	1
β-strand	306	1	3
α-helix	307-313	7
α-helix	317-328	12
β-strand	330-331	2	8
α-helix	332-333	2
α-helix	338-354	17
α-helix	359-1025	18
α-helix	1032-1035	4
α-helix	1036-1041	6
α-helix	1042-1051	10
α-helix	1053-1055	3
α-helix	1059-1079	21
α-helix	1087-1100	14
α-helix	2034-2054	21
α-helix	2056-2058	3
β-strand	2064-2065	2	9
α-helix	2066-2067	2
β-strand	2068-2069	2	10
β-strand	2074-2075	2	10
β-strand	2078-2079	2	9
β-strand	2082-2087	6	11
α-helix	2088-2089	2
β-strand	2095	1	12
β-strand	2100-2105	6	11
β-strand	2111	1	11
β-strand	2113	1	13
β-strand	2120	1	13
β-strand	2123	1	11
α-helix	2125-2127	3
β-strand	2128	1	12
α-helix	2132-2142	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Maltose/maltodextrin-binding periplasmic protein,Receptor activity-modifying protein 1,Calcitonin…	A	protein	593	Escherichia coli K-12, Homo sapiens	O60894 (AlphaFold model), P0AEX9 (AlphaFold model), Q16602 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8AX6_1 Maltose/maltodextrin-binding periplasmic protein,Receptor activity-modifying protein 1,Calcitonin gene-related peptide type 1 receptor (chains A)
SAKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVAATGDGPD
IIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNGKLIAYPIAVEALSLIYN
KDLLPNPPKTWEEIPALDKELKAKGKSALMFNLQEPYFTWPLIAADGGYAFKYENGKYDI
KDVGVDNAGAKAGLTFLVDLIKNKHMNADTDYSIAEAAFNKGETAMTINGPWAWSNIDTS
KVNYGVTVLPTFKGQPSKPFVGVLSAGINAASPNKELAKEFLENYLLTDEGLEAVNKDKP
LGAVALKSYEEELAKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINAASGRQTVD
EALKDAQTNAAAEFTTACQEANYGALLRELCLTQFQVDMEAVGETLWCDWGRTIRSYREL
ADCTWHMAEKLGCFWPNAEVDRFFLAVHGRYFRSCPISGRAVGSAGSAGSAEDSIQLGVT
RNKIMTAQYECYQKIMQDPIQQAEGVYCQRTWDGWLCWNDVAAGTESMQLCPDYFQDFDP
SEKVTKICDQDGNWFRHPASQRTWTNYTQCNVNTHEKVKTALNLFYLHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
OP9	(1~{S},10~{R},20~{E})-12-methyl-10-[(7-methyl-2~{H}-indazol-5-yl)methyl]-15,18-…	C35 H36 N6 O5	1

Water and common crystallization additives (PG4) are not listed.

Primary citation

Novel Macrocyclic Antagonists of the CGRP Receptor Part 2: Stereochemical Inversion Induces an Unprecedented Binding Mode. Southall, S.M., Banerjee, J., Brown, J. et al. ACS Med Chem Lett (2022) 13:1776-1782. DOI 10.1021/acsmedchemlett.2c00400 · PubMed

Other PDB entries of the same protein (UniProt O60894 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6ZHO 1.6 Å, Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity…
8AX7 1.65 Å, Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic…
7P0F 1.85 Å, Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic…
6D1U 2.05 Å, Crystal structure of the human CLR:RAMP1 extracellular domain heterodimer in complex…
3N7S 2.1 Å, Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR,…
7TYF 2.2 Å, Human Amylin1 Receptor in complex with Gs and rat amylin peptide
9BP3 2.2 Å, Human Amylin1 Receptor in complex with Gs and cagrilintide
7P0I 2.3 Å, Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic…
2YX8 2.4 Å, Crystal structure of the extracellular domain of human RAMP1
9AUC 2.4 Å, Human Amylin1 Receptor in Complex with Gs and human Calcitonin Gene-Related Peptide
4RWG 2.44 Å, Crystal structure of the CLR:RAMP1 extracellular domain heterodimer with bound high…
6UMG 2.7 Å, Crystal structure of erenumab Fab bound to the extracellular domain of CGRP receptor

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