3G04

Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3g04a1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3g04b_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3g04c_	Alpha and beta proteins (a/b)	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	L domain-like	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
C	SCOP2B Superfamily	L domain-like	8078984	3001010	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF07654	e3g04A2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07654	ECOD (1.6)
A	PF07686	e3g04A1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
B	PF07654	e3g04B2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07654	ECOD (1.6)
B	PF07686	e3g04B1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
C	PF13855	e3g04C1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: PF13855	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
A	Thyroid-stimulating human monoclonal autoantibody (M22)	L-LAMBDA	Homo sapiens (human)	IGLV1-3601, TRBJ2-101, TRBJ2-301, IGLC303	V-DOMAIN V-LAMBDA, C-DOMAIN C-LAMBDA	IG	FAB-GAMMA-1_LAMBDA	IMGT (202418-0)
B	Thyroid-stimulating human monoclonal autoantibody (M22)	VH-CH1	Homo sapiens (human)	IGHV5-10-103, IGHV5-10-101, IGHJ501, IGHG101, IGHG102, IGHG104	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_LAMBDA	IMGT (202418-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
A	Light Chain	IGLV1	Lambda	thyrotropin receptor	SAbDab (2024-05-10)
B	Heavy Chain	IGHV5	-	thyrotropin receptor	SAbDab (2024-05-10)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C	PF13306	BspA type Leucine rich repeat region (6 copies) (LRR_5)	BspA type Leucine rich repeat region (6 copies)	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	HUMAN THYROID STIMULATING AUTOANTIBODY M22 LIGHT CHAIN	-	-	-
B	HUMAN THYROID STIMULATING AUTOANTIBODY M22 HEAVY CHAIN	-	-	-
C	Thyrotropin receptor	molecular transducer activity signaling receptor activity protein-hormone receptor activity G protein-coupled receptor activity transmembrane signaling receptor activity thyroid-stimulating hormone receptor activity protein-containing complex binding binding peptide receptor activity G protein-coupled peptide receptor activity	cellular response to stimulus cellular response to nitrogen compound response to organic substance response to stimulus response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to thyrotropin-releasing hormone cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to chemical stimulus cellular response to organonitrogen compound cellular response to stimulus cellular response to nitrogen compound response to organic substance response to stimulus response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to thyrotropin-releasing hormone cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to chemical stimulus cellular response to organonitrogen compound response to thyrotropin-releasing hormone response to hormone response to chemical cellular process cellular response to organic substance cellular response to hormone stimulus regulation of biological process regulation of cellular process signaling biological regulation hormone-mediated signaling pathway cell communication signal transduction cell-cell signaling adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway response to glycoprotein cellular response to glycoprotein cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation positive regulation of biological process positive regulation of cellular process multicellular organismal process homeostatic process adaptive thermogenesis positive regulation of metabolic process multicellular organismal-level homeostasis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis positive regulation of cold-induced thermogenesis positive regulation of multicellular organismal process metabolic process regulation of multicellular organismal process regulation of metabolic process cell surface receptor signaling pathway G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger thyroid-stimulating hormone signaling pathway	cell surface cellular anatomical entity cell periphery plasma membrane membrane basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane protein-containing complex receptor complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C	IPR002274	Thyrotropin receptor	Family
C	IPR000276	G protein-coupled receptor, rhodopsin-like	Family
C	IPR002131	Glycoprotein hormone receptor family	Family
C	IPR026906	BspA-type LRR region	Repeat
C	IPR017452	GPCR, rhodopsin-like, 7TM	Domain
C	IPR032675	Leucine-rich repeat domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C	Pharos: P16473	Graves disease congenital hypothyroidism hyperthyroidism thyrotoxicosis familial hyperthyroidism due to mutations in TSH receptor Hashimoto thyroiditis familial gestational hyperthyroidism thyroid hypoplasia hypothyroidism hypothyroidism due to TSH receptor mutations adenoma microcystic adenoma papillary adenoma sarcomatoid carcinoma Lymphatic Metastasis Graves disease congenital hypothyroidism hyperthyroidism thyrotoxicosis familial hyperthyroidism due to mutations in TSH receptor Hashimoto thyroiditis familial gestational hyperthyroidism thyroid hypoplasia hypothyroidism hypothyroidism due to TSH receptor mutations adenoma microcystic adenoma papillary adenoma sarcomatoid carcinoma Lymphatic Metastasis follicular thyroid adenoma adrenal gland cancer thyroid adenoma carcinoma thyroid gland carcinoma goiter malignant ependymoma athyreosis exophthalmos intellectual disability thyroid cancer facioscapulohumeral muscular dystrophy undifferentiated carcinoma lung benign neoplasm malignant colon neoplasm medulloblastoma osteosarcoma psoriasis astrocytic tumor thyroiditis

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.