7f58

Cryo-EM structure of THIQ-MC4R-Gs_Nb35 complex

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 5	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092-2） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P62873） Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P59768） Nanobody35 × 1 ;(3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxidanylidene-propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide ; × 1 CALCIUM ION × 1 water × 2	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 3–334； UniProt 1–332

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

Homo sapiens

UniProt P63092-2

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 5	Melanocortin receptor 4 × 1 （P32245） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P62873） Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P59768） Nanobody35 × 1 ;(3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxidanylidene-propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide ; × 1 CALCIUM ION × 1 water × 2	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GNAS2-2_HUMAN
Isoform	—
PDB entities	2
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

Homo sapiens

UniProt P62873

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 5	Melanocortin receptor 4 × 1 （P32245） Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092-2） Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P59768） Nanobody35 × 1 ;(3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxidanylidene-propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide ; × 1 CALCIUM ION × 1 water × 2	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GBB1_HUMAN
Isoform	—
PDB entities	3
Chains and sequence ranges	Author chain B； PDBConstruct 20–358； UniProt 2–340

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

Homo sapiens

UniProt P59768

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 5	Melanocortin receptor 4 × 1 （P32245） Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092-2） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P62873） Nanobody35 × 1 ;(3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxidanylidene-propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide ; × 1 CALCIUM ION × 1 water × 2	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GBG2_HUMAN
Isoform	—
PDB entities	4
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	7f58
Deposition date deposition_date	2021-06-21
Structure title title	Cryo-EM structure of THIQ-MC4R-Gs_Nb35 complex
Keywords keywords	single particle, membrane protein, Class A G-protein-coupled receptors; MEMBRANE 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.

7f58__assembly_1__model_1

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

Download this curve (.dat)

7f58__assembly_1__model_1 | I(q)

100 plotted points; both axes use logarithmic scales.

7f58__assembly_1__model_1 | P(r) · Pending

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

Rg（Guinier）	33.84 Å
Rg (electron density)	33.79 Å
Total Rg	34.33 Å
Atom count	8058
Residues	1021
Excluded volume	143910 Å³
Maximum q	0.500 Å⁻¹

Assembly	Model	Structure unit	Oligomeric description	Status	CRYSOL	Actions
1	1	`7f58__assembly_1__model_1`	pentameric （5）	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	56053.2 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	8065

GPMVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPLIYALRSQELRKTFKEIICCYPLGGLCDLSSRYGGSGGSVFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLITPDGSMLFRVTINSGGSLEVLFQ

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera frugiperda

Entity 2 Entity 2 polymer

Description description	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Molecular weight formula_weight	44284.1 kDa
Mutation mutation	S54N, G226A, E268A, N271K, K274D, R280K, T284D, I287T
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A

MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQMRILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera frugiperda

Entity 3 Entity 3 polymer

Description description	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Molecular weight formula_weight	41729.6 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	B

MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGGGGSSGVSGWRLFKKIS

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera frugiperda

Entity 4 Entity 4 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	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera frugiperda

Entity 5 Entity 5 polymer

Description description	Nanobody35
Molecular weight formula_weight	13711.3 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	N

QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQGTQVTV

Source Source

Source organism organism	synthetic construct
NCBI taxonomy ID ncbi_taxonomy_id	32630
Host organism host_organism	Escherichia coli

Entity 6 Entity 6 non-polymer

Description description	;(3R)-N-[(2R)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxidanylidene-propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide ;
Molecular weight formula_weight	589.2 kDa
Source method src_method	syn
Copy count entity_count	1

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	7

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6. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

Domain ID domain_id	7f58B01
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	7f58N01
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	3.10 Å
Resolution测定Method resolution_method	—
颗粒数 num_particles	269832

Cryo-EM structure of THIQ-MC4R-Gs_Nb35 complex

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

7f58__assembly_1__model_1

7f58__assembly_1__model_1 | I(q)

7f58__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

Source Source

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 non-polymer

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)