7piu

Cryo-EM structure of the agonist setmelanotide bound to the active melanocortin-4 receptor (MC4R) in complex with the heterotrimeric Gs protein at 2.6 A resolution.

Method: ELECTRON MICROSCOPY

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1. Protein Identity and Related Structures Protein Identity & Related Structures

Melanocortin receptor 4

Homo sapiens

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 6	Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree) × 1 Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P54311） Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P63212） Camelid antibody fragment - nanobody 35 × 1 CALCIUM ION × 1 water × 6	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	MC4R_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain R； PDBConstruct 9–340； UniProt 1–332

Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

Homo sapiens

UniProt P63092

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 6	Melanocortin receptor 4 × 1 （P32245） Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree) × 1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P54311） Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P63212） Camelid antibody fragment - nanobody 35 × 1 CALCIUM ION × 1 water × 6	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GNAS2_HUMAN
Isoform	P63092-2
PDB entities	3
Chains and sequence ranges	Author chain A； PDBConstruct 1–380； UniProt 1–380

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

Rattus norvegicus

UniProt P54311

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 6	Melanocortin receptor 4 × 1 （P32245） Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree) × 1 Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092） Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P63212） Camelid antibody fragment - nanobody 35 × 1 CALCIUM ION × 1 water × 6	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GBB1_RAT
Isoform	—
PDB entities	4
Chains and sequence ranges	Author chain B； PDBConstruct 7–345； UniProt 2–340

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

Bos taurus

UniProt P63212

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 6	Melanocortin receptor 4 × 1 （P32245） Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree) × 1 Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P54311） Camelid antibody fragment - nanobody 35 × 1 CALCIUM ION × 1 water × 6	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GBG2_BOVIN
Isoform	—
PDB entities	5
Chains and sequence ranges	Author chain G； PDBConstruct 1–71； UniProt 1–71

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	7piu
Deposition date deposition_date	2021-08-23
Structure title title	Cryo-EM structure of the agonist setmelanotide bound to the active melanocortin-4 receptor (MC4R) in complex with the heterotrimeric Gs protein at 2.6 A resolution.
Keywords keywords	;GPCR, MELANOCORTIN-4 RECEPTOR, MELANOCORTIN RECEPTORS, SETMELANOTIDE, NDP-ALPHA-MSH, ALPHA-MSH, ANTAGONISM, AGONISM, APPETITE REGULATION, ANTI-OBESITY TREATMENT, SIGNALING PROTEIN ;; SIGNALING PROTEIN
Experimental Method method	ELECTRON MICROSCOPY

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3. Official assembly/model SAXS Official SAXS Profiles

This page reads only the latest assembly calculations. Every curve maps to an explicit PDB entry, official biological assembly and coordinate model.

7piu__assembly_1__model_1

Assembly 1 · Model 1 · CRYSOL 4.1.3-1-20251215 (887e7ef)

Download this curve (.dat)

7piu__assembly_1__model_1 | I(q)

100 plotted points; both axes use logarithmic scales.

7piu__assembly_1__model_1 | P(r) · Pending

P(r) will be calculated and displayed separately for the same assembly/model.

Rg（Guinier）	33.66 Å
Rg (electron density)	33.60 Å
Total Rg	34.17 Å
Atom count	7584
Residues	974
Excluded volume	135580 Å³
Maximum q	0.500 Å⁻¹

Assembly	Model	Structure unit	Oligomeric description	Status	CRYSOL	Actions
1	1	`7piu__assembly_1__model_1`	hexameric （6）	Success	4.1.3-1-20251215 (887e7ef)	View Download

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4. Crystallography and Experiment 4. Crystallography & Experiment

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5. Entities and Polymers Entities & Polymers (8)

Entity 1 Entity 1 polymer

Description description	Melanocortin receptor 4
Molecular weight formula_weight	38698.5 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	R
Atom count atom_count	7788

DYKDDDDKMVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPLIYALRSQELRKTFKEIICCYPLGGLCDLSSRYLEVLFQ

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera aff. frugiperda 1 BOLD-2017

Entity 2 Entity 2 polymer

Description description	Setmelanotide (other names RM-493; BIM-22493; IRC-022493; Imcivree)
Molecular weight formula_weight	1081.3 kDa
Source method src_method	syn
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	P

RCAHFRWC

Entity 3 Entity 3 polymer

Description description	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Molecular weight formula_weight	44326.2 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A

MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQMRILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Trichoplusia ni

Entity 4 Entity 4 polymer

Description description	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Molecular weight formula_weight	37728.2 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	B

GPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Source Source

Source organism organism	Rattus norvegicus
Common name common_name	Rat
NCBI taxonomy ID ncbi_taxonomy_id	10116
Host organism host_organism	Trichoplusia ni

Entity 5 Entity 5 polymer

Description description	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Molecular weight formula_weight	7861.1 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	G

MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFREKKFFCAIL

Source Source

Source organism organism	Bos taurus
Common name common_name	Bovine
NCBI taxonomy ID ncbi_taxonomy_id	9913
Host organism host_organism	Trichoplusia ni

Entity 6 Entity 6 polymer

Description description	Camelid antibody fragment - nanobody 35
Molecular weight formula_weight	14714.3 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	N

QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQGTQVTVSSHHHHHH

Source Source

Source organism organism	Lama glama
NCBI taxonomy ID ncbi_taxonomy_id	9844
Host organism host_organism	Escherichia coli

Entity 7 Entity 7 non-polymer

Description description	CALCIUM ION
Molecular weight formula_weight	40.1 kDa
Source method src_method	syn
Copy count entity_count	1

Entity 8 Entity 8 water

Description description	water
Molecular weight formula_weight	18.0 kDa
Source method src_method	nat
Copy count entity_count	88

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6. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

Domain ID domain_id	7piuB01
Class class	2 — Mainly Beta
Architecture architecture	130 — 7 Propeller
Topology topology	10 — Methylamine Dehydrogenase; Chain H
Homologous superfamily homologous superfamily	10 — YVTN repeat-like/Quinoprotein amine dehydrogenase

Domain ID domain_id	7piuN01
Class class	2 — Mainly Beta
Architecture architecture	60 — Sandwich
Topology topology	40 — Immunoglobulin-like
Homologous superfamily homologous superfamily	10 — Immunoglobulins

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Unit-cell length a length_a	1.000 Å
Unit-cell length b length_b	1.000 Å
Unit-cell length c length_c	1.000 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	90.00 °
Unit-cell angle γ angle_gamma	90.00 °
Molecules per unit cell Z z_pdb	—

Space group space_group	P 1
Space-group number int_tables_number	1
Crystal system crystal_system	—

Resolution resolution	2.58 Å
Resolution测定Method resolution_method	—
颗粒数 num_particles	370621

Cryo-EM structure of the agonist setmelanotide bound to the active melanocortin-4 receptor (MC4R) in complex with the heterotrimeric Gs protein at 2.6 A resolution.

1. Protein Identity and Related Structures Protein Identity & Related Structures

Melanocortin receptor 4

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

2. Structure Basics 2. Structure Basics

3. Official assembly/model SAXS Official SAXS Profiles

7piu__assembly_1__model_1

7piu__assembly_1__model_1 | I(q)

7piu__assembly_1__model_1 | P(r) · Pending

4. Crystallography and Experiment 4. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

冷冻电镜 EM 3D

5. Entities and Polymers Entities & Polymers (8)

Entity 1 Entity 1 polymer

Polymer Polymer

Source Source

Entity 2 Entity 2 polymer

Polymer Polymer

Entity 3 Entity 3 polymer

Polymer Polymer

Source Source

Entity 4 Entity 4 polymer

Polymer Polymer

Source Source

Entity 5 Entity 5 polymer

Polymer Polymer

Source Source

Entity 6 Entity 6 polymer

Polymer Polymer

Source Source

Entity 7 Entity 7 non-polymer

Entity 8 Entity 8 water

6. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

7. Citations (1)