5J13

Structural basis for TSLP antagonism by the therapeutic antibody Tezepelumab (MEDI9929 / AMG-157)

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Thera-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)
B	d5j13b1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d5j13b2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF15216	e5j13A1	A: alpha bundles	X: Ferritin/Heme oxygenase/4-helical cytokines	H: 4-helical cytokines (From Topology)	T: 4-helical cytokines	F: PF15216	ECOD (1.6)
B	PF07654	e5j13B2	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	e5j13B1	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	PF07654	e5j13C1	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)
C	PF07686	e5j13C2	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)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.1250.90	Mainly Alpha	Up-down Bundle	Growth Hormone	Chain: A	CATH (4.3.0)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	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
B	Antibody Fab Fragment, anti-TSLP	L-LAMBDA	Homo sapiens (human)	IGLV3-2102, IGLJ201, IGLJ301, IGLC201, IGLC202, IGLC304	V-DOMAIN V-LAMBDA, C-DOMAIN C-LAMBDA	IG	FAB-GAMMA-2_LAMBDA	IMGT (202416-0)
C	Antibody Fab Fragment, anti-TSLP	VH-CH1	Homo sapiens (human)	IGHV3-3301, IGHV3-3304, IGHJ302, IGHG201, IGHG206, IGHG205, IGHG2*03	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-2_LAMBDA	IMGT (202416-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
B	Light Chain	IGLV3	Lambda	thymic stromal lymphopoietin	SAbDab (2024-04-26)
C	Heavy Chain	IGHV3	-	thymic stromal lymphopoietin	SAbDab (2024-04-26)

Thera-SAbDab Antibody Annotation Thera-SAbDab Database Homepage

Chain	Name	Target	Provenance Source
B	Tezepelumab	TSLP	Therapeutic SAbDab (2024-04-26)
C	Tezepelumab	TSLP	Therapeutic SAbDab (2024-04-26)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF15216	Thymic stromal lymphopoietin (TSLP)	Thymic stromal lymphopoietin	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Thymic stromal lymphopoietin	protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity cytokine activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity cytokine receptor binding growth factor receptor binding interleukin-7 receptor binding	regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process multicellular organismal process cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process multicellular organismal process cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of interleukin-5 production organic substance metabolic process positive regulation of biosynthetic process regulation of cytokine production organic substance biosynthetic process cytokine production regulation of multicellular organismal process positive regulation of macromolecule metabolic process interleukin-5 production regulation of biosynthetic process cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process positive regulation of cytokine production regulation of metabolic process positive regulation of interleukin-5 production positive regulation of cellular biosynthetic process regulation of chemokine production chemokine production positive regulation of chemokine production positive regulation of mast cell activation regulation of leukocyte activation cell activation regulation of cell activation myeloid leukocyte activation leukocyte activation positive regulation of cell activation immune system process positive regulation of leukocyte activation mast cell activation regulation of mast cell activation regulation of immune system process positive regulation of immune system process regulation of defense response response to stimulus regulation of response to external stimulus defense response response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus regulation of response to stress response to stress positive regulation of defense response inflammatory response humoral immune response biological process involved in interspecies interaction between organisms response to other organism immune response defense response to symbiont antimicrobial humoral response response to biotic stimulus antimicrobial humoral immune response mediated by antimicrobial peptide defense response to other organism response to external biotic stimulus cellular response to stimulus positive regulation of phosphorylation positive regulation of phosphate metabolic process cell communication regulation of primary metabolic process regulation of phosphate metabolic process peptidyl-amino acid modification phosphate-containing compound metabolic process signal transduction protein modification process phosphorus metabolic process positive regulation of protein phosphorylation tyrosine phosphorylation of STAT protein protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process macromolecule modification regulation of phosphorus metabolic process cell surface receptor signaling pathway via STAT regulation of protein modification process signaling regulation of protein phosphorylation positive regulation of protein metabolic process peptidyl-tyrosine modification positive regulation of peptidyl-tyrosine phosphorylation positive regulation of protein modification process protein metabolic process organonitrogen compound metabolic process cell surface receptor signaling pathway regulation of tyrosine phosphorylation of STAT protein regulation of peptidyl-tyrosine phosphorylation positive regulation of tyrosine phosphorylation of STAT protein regulation of phosphorylation peptidyl-tyrosine phosphorylation cell surface receptor signaling pathway via JAK-STAT defense response to fungus response to fungus interleukin-10 production regulation of interleukin-10 production positive regulation of interleukin-10 production positive regulation of cell communication positive regulation of signal transduction positive regulation of receptor signaling pathway via STAT regulation of signal transduction regulation of signaling regulation of cell communication regulation of receptor signaling pathway via STAT positive regulation of signaling negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of macrophage colony-stimulating factor production positive regulation of granulocyte colony-stimulating factor production regulation of granulocyte colony-stimulating factor production positive regulation of macrophage colony-stimulating factor production granulocyte colony-stimulating factor production macrophage colony-stimulating factor production interleukin-13 production positive regulation of interleukin-13 production regulation of interleukin-13 production interleukin-6 production positive regulation of interleukin-6 production regulation of interleukin-6 production regulation of chemokine (C-C motif) ligand 1 production positive regulation of chemokine (C-C motif) ligand 1 production chemokine (C-C motif) ligand 1 production defense response to Gram-negative bacterium defense response to bacterium response to bacterium response to organic substance response to cytokine positive regulation of response to cytokine stimulus cytokine-mediated signaling pathway cellular response to cytokine stimulus cellular response to organic substance regulation of cytokine-mediated signaling pathway regulation of response to cytokine stimulus cellular response to chemical stimulus response to chemical positive regulation of cytokine-mediated signaling pathway	extracellular region cellular anatomical entity extracellular space
B	anti-TSLP Fab-fragment, light chain	-	-	-
C	anti-TSLP Fab-fragment, heavy chain	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR038329	Thymic stromal lymphopoietin superfamily	Homologous Superfamily
A	IPR029189	Thymic stromal lymphopoietin	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q969D9	asthma eosinophilic esophagitis Albuminuria membranoproliferative glomerulonephritis pancreatic intraductal papillary-mucinous carcinoma rhinitis common cold dermatitis hepatocellular carcinoma invasive ductal breast carcinoma primary membranoproliferative glomerulonephritis allergic disease atopic eczema cystic fibrosis dermatitis, atopic asthma eosinophilic esophagitis Albuminuria membranoproliferative glomerulonephritis pancreatic intraductal papillary-mucinous carcinoma rhinitis common cold dermatitis hepatocellular carcinoma invasive ductal breast carcinoma primary membranoproliferative glomerulonephritis allergic disease atopic eczema cystic fibrosis dermatitis, atopic hypereosinophilic syndrome nasal cavity disease allergic rhinitis breast cancer dense deposit disease ductal breast carcinoma in situ eosinophilic granulomatosis with polyangiitis

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.