6NHA

Crystal structure of SYNT001, a human FcRn blocking monoclonal antibody

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
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)
A	d6nhaa2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d6nhaa1	Alpha and beta proteins (a+b)	MHC antigen-recognition domain	MHC antigen-recognition domain	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d6nhab_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	beta2-microglobulin	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth L]	d6nhal2	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)
C [auth L]	d6nhal1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth H]	d6nhah_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	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)
A	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8054653	3000071	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	MHC antigen-recognition domain	8034816	3000521	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8003766	3000071	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	C1-set_2	e6nhaA2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_2	ECOD (1.6)
A	MHC_I	e6nhaA1	A: a+b two layers	X: MHC antigen-recognition domain (From Topology)	H: MHC antigen-recognition domain (From Topology)	T: MHC antigen-recognition domain	F: MHC_I	ECOD (1.6)
B	C1-set_2	e6nhaB1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_2	ECOD (1.6)
C [auth L]	C1-set_4	e6nhaL1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
C [auth L]	V-set	e6nhaL2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
D [auth H]	V-set_8	e6nhaH2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
D [auth H]	C1-set_1	e6nhaH1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.500.10	Alpha Beta	2-Layer Sandwich	Murine Class I Major Histocompatibility Complex, H2-DB	Chain A, domain 1	CATH (utative)
A	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (utative)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (utative)
C [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (utative)
D [auth H]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (utative)

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	FCGRT (FcRn, neonatal Fc receptor large subunit p51)	I-ALPHA-LIKE	Homo sapiens (human)	FCGRT*01	G-DOMAIN G-ALPHA1-LIKE, G-DOMAIN G-ALPHA2-LIKE, C-LIKE-DOMAIN C-LIKE	MH	MH1LIKE-ALPHA-LIKE_B2M	IMGT (202415-0)
B	FCGRT (FcRn, neonatal Fc receptor large subunit p51)	B2M	Homo sapiens (human)	B2M01, B2M02	C-LIKE-DOMAIN C-LIKE	MH	MH1LIKE-ALPHA-LIKE_B2M	IMGT (202415-0)
C [auth L]	mAb SYNT001, anti- FcRn	L-KAPPA	Chimeric (chimeric)	IGKV13-8501, IGKJ201, IGKC*01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-4_KAPPA	IMGT (202415-0)
D [auth H]	mAb SYNT001, anti- FcRn	VH-CH1	Chimeric (chimeric)	IGHV1-8101, IGHJ103, IGHG401, IGHG404	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-4_KAPPA	IMGT (202415-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
C [auth L]	Light Chain	IGKV13	Kappa	igg receptor fcrn large subunit p51 \| beta-2-microglobulin	SAbDab (2024-04-19)
D [auth H]	Heavy Chain	IGHV1	-	igg receptor fcrn large subunit p51 \| beta-2-microglobulin	SAbDab (2024-04-19)

Thera-SAbDab Antibody Annotation Thera-SAbDab Database Homepage

Chain	Name	Target	Provenance Source
C [auth L]	Orilanolimab	FCGRT/FcRn	Therapeutic SAbDab (2024-04-19)
D [auth H]	Orilanolimab	FCGRT/FcRn	Therapeutic SAbDab (2024-04-19)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain
B	PF07654	Immunoglobulin C1-set domain (C1-set)	Immunoglobulin C1-set domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	IgG receptor FcRn large subunit p51	protein-containing complex binding binding immunoglobulin binding IgG binding beta-2-microglobulin binding protein binding	localization multicellular organismal process transport IgG immunoglobulin transcytosis in epithelial cells mediated by FcRn immunoglobulin receptor cellular process establishment of localization immunoglobulin transcytosis in epithelial cells transcytosis vesicle-mediated transport response to stimulus immune response immune system process	cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane endosome membrane membrane-bounded organelle intracellular anatomical structure endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane endosome membrane membrane-bounded organelle intracellular anatomical structure endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane cytoplasmic vesicle organelle cytoplasm vesicle organelle membrane extracellular region extracellular space
B	Beta-2-microglobulin	binding antigen binding peptide antigen binding peptide binding protein-containing complex binding MHC protein complex binding MHC class II protein complex binding identical protein binding protein binding protein homodimerization activity protein dimerization activity structural molecule activity	intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis protein refolding organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process intracellular iron ion homeostasis inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis protein refolding organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process primary metabolic process gene expression macromolecule biosynthetic process protein maturation organic substance metabolic process protein folding biosynthetic process organic substance biosynthetic process metabolic process cellular process protein metabolic process macromolecule metabolic process adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains multicellular organismal process regulation of immune effector process lymphocyte mediated immunity T cell mediated immunity positive regulation of leukocyte mediated immunity regulation of cellular process response to stimulus T cell cytokine production positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of immune response cytokine production leukocyte mediated immunity regulation of immune system process positive regulation of macromolecule metabolic process positive regulation of adaptive immune response positive regulation of T cell cytokine production positive regulation of immune system process regulation of T cell mediated immunity regulation of biological process regulation of cytokine production involved in immune response immune response regulation of adaptive immune response regulation of cellular metabolic process immune effector process regulation of gene expression regulation of leukocyte mediated immunity regulation of response to stimulus positive regulation of production of molecular mediator of immune response positive regulation of multicellular organismal process regulation of immune response regulation of macromolecule biosynthetic process regulation of production of molecular mediator of immune response positive regulation of cytokine production regulation of metabolic process positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity positive regulation of biological process positive regulation of cellular metabolic process positive regulation of response to stimulus regulation of T cell cytokine production regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of biosynthetic process regulation of cytokine production positive regulation of immune effector process regulation of multicellular organismal process cytokine production involved in immune response positive regulation of cellular process production of molecular mediator of immune response regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process adaptive immune response regulation of cellular biosynthetic process regulation of lymphocyte mediated immunity positive regulation of gene expression immune system process positive regulation of T cell mediated immunity positive regulation of cytokine production involved in immune response positive regulation of cellular biosynthetic process cellular response to stimulus cellular response to inorganic substance cellular response to metal ion response to inorganic substance cellular response to iron ion cellular response to chemical stimulus response to metal ion response to chemical response to iron ion cellular response to iron(III) ion response to iron(III) ion multicellular organismal-level iron ion homeostasis multicellular organismal-level homeostasis multicellular organismal-level chemical homeostasis regulation of neuron projection development regulation of cellular component organization cellular developmental process cell projection organization negative regulation of biological process cell development neuron projection development cellular component organization neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development negative regulation of cellular process cellular component organization or biogenesis negative regulation of cell projection organization system development developmental process plasma membrane bounded cell projection organization negative regulation of cellular component organization regulation of cell projection organization nervous system development negative regulation of neuron projection development generation of neurons neuron development regulation of plasma membrane bounded cell projection organization positive regulation of protein binding regulation of binding positive regulation of binding regulation of protein binding positive regulation of molecular function regulation of molecular function regulation of receptor binding regulation of transferrin receptor binding positive regulation of receptor binding positive regulation of transferrin receptor binding regulation of developmental process regulation of cell differentiation regulation of cell development myeloid cell homeostasis erythrocyte homeostasis regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation erythrocyte differentiation regulation of erythrocyte differentiation myeloid cell differentiation regulation of hemopoiesis homeostasis of number of cells antigen processing and presentation antigen processing and presentation of peptide antigen via MHC class Ib antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent antigen processing and presentation via MHC class Ib antigen processing and presentation of exogenous peptide antigen via MHC class Ib antigen processing and presentation of exogenous peptide antigen antigen processing and presentation of peptide antigen antigen processing and presentation of exogenous antigen cell activation mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation T cell differentiation leukocyte differentiation regulation of localization import into cell positive regulation of cellular component organization transport vesicle-mediated transport localization positive regulation of endocytosis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of transport regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport establishment of localization positive regulation of transport endocytosis receptor-mediated endocytosis peptide antigen assembly with MHC class I protein complex protein-containing complex organization peptide antigen assembly with MHC protein complex MHC class I protein complex assembly cellular component biogenesis cellular component assembly protein-containing complex assembly antigen processing and presentation of peptide antigen via MHC class I MHC protein complex assembly regulation of neurogenesis regulation of nervous system development negative regulation of neurogenesis negative regulation of nervous system development negative regulation of cell differentiation negative regulation of developmental process negative regulation of cell development negative regulation of multicellular organismal process positive regulation of ferrous iron binding regulation of ferrous iron binding negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation regulation of epithelial cell proliferation epithelial cell proliferation negative regulation of epithelial cell proliferation positive regulation of leukocyte mediated cytotoxicity T cell mediated cytotoxicity positive regulation of T cell mediated cytotoxicity regulation of leukocyte mediated cytotoxicity leukocyte mediated cytotoxicity regulation of T cell mediated cytotoxicity regulation of cell killing positive regulation of cell killing cell killing iron ion transport transition metal ion transport monoatomic ion transport monoatomic cation transport metal ion transport system process sensory perception of chemical stimulus sensory perception nervous system process sensory perception of smell amyloid fibril formation supramolecular fiber organization protein homotetramerization protein complex oligomerization protein tetramerization protein homooligomerization antigen processing and presentation of exogenous peptide antigen via MHC class II antigen processing and presentation of peptide or polysaccharide antigen via MHC class II antigen processing and presentation of peptide antigen via MHC class II negative regulation of receptor binding negative regulation of protein binding negative regulation of binding negative regulation of molecular function peptide antigen assembly with MHC class II protein complex MHC class II protein complex assembly cellular response to nicotine response to nicotine regulation of cellular senescence cellular senescence positive regulation of cellular senescence cellular response to stress response to stress antigen processing and presentation of endogenous peptide antigen antigen processing and presentation of endogenous antigen antigen processing and presentation of endogenous peptide antigen via MHC class I behavior learning or memory cognition regulation of leukocyte activation regulation of cell activation positive regulation of leukocyte cell-cell adhesion leukocyte cell-cell adhesion positive regulation of cell-cell adhesion positive regulation of lymphocyte activation positive regulation of cell activation cell adhesion cell-cell adhesion positive regulation of leukocyte activation regulation of cell-cell adhesion positive regulation of T cell activation positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation regulation of leukocyte cell-cell adhesion regulation of lymphocyte activation negative regulation of forebrain neuron differentiation forebrain development regulation of forebrain neuron differentiation central nervous system neuron differentiation head development forebrain generation of neurons animal organ development brain development central nervous system development forebrain neuron differentiation negative regulation of neuron differentiation regulation of neuron differentiation regulation of monoatomic ion transport regulation of iron ion transport regulation of metal ion transport response to organic substance biological process involved in interspecies interaction between organisms response to other organism response to bacterium response to external stimulus response to external biotic stimulus response to molecule of bacterial origin response to biotic stimulus	cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex HFE-transferrin receptor complex receptor complex intracellular anatomical structure cytoplasm cytosol MHC class I protein complex MHC protein complex endosome membrane endosome intracellular vesicle late endosome membrane intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane late endosome organelle membrane phagocytic vesicle phagocytic vesicle membrane endocytic vesicle membrane endocytic vesicle vacuolar membrane lytic vacuole vacuole lytic vacuole membrane lysosomal membrane lysosome Golgi apparatus membrane-enclosed lumen intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endoplasmic reticulum Golgi membrane MHC class I peptide loading complex organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum protein-containing complex endoplasmic reticulum membrane vesicle lumen cytoplasmic vesicle lumen secretory granule lumen specific granule lumen secretory granule secretory vesicle specific granule anchoring junction cell junction focal adhesion cell-substrate junction MHC class II protein complex early endosome endosome lumen early endosome lumen recycling endosome recycling endosome membrane tertiary granule lumen tertiary granule early endosome membrane transport vesicle transport vesicle membrane coated vesicle membrane COPII-coated ER to Golgi transport vesicle ER to Golgi transport vesicle membrane coated vesicle
C [auth L]	SYNT001-Fab light chain	-	-	-
D [auth H]	SYNT001-Fab heavy chain	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
A	IPR037055	MHC class I-like antigen recognition-like superfamily	Homologous Superfamily
A	IPR003597	Immunoglobulin C1-set	Domain
A	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A	IPR011161	MHC class I-like antigen recognition-like	Domain
A	IPR011162	MHC classes I/II-like antigen recognition protein	Homologous Superfamily
A	IPR007110	Immunoglobulin-like domain	Domain
A	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site
B	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
B	IPR003006	Immunoglobulin/major histocompatibility complex, conserved site	Conserved Site
B	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
B	IPR007110	Immunoglobulin-like domain	Domain
B	IPR003597	Immunoglobulin C1-set	Domain
B	IPR015707	Beta-2-Microglobulin	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P55899	systemic lupus erythematosus tuberculosis adrenal cortex carcinoma Crohn disease glioblastoma malignant ependymoma myasthenia gravis pilocytic astrocytoma rheumatoid arthritis systemic sclerosis ulcerative colitis astrocytic tumor ductal breast carcinoma in situ Hodgkins lymphoma malignant glioma systemic lupus erythematosus tuberculosis adrenal cortex carcinoma Crohn disease glioblastoma malignant ependymoma myasthenia gravis pilocytic astrocytoma rheumatoid arthritis systemic sclerosis ulcerative colitis astrocytic tumor ductal breast carcinoma in situ Hodgkins lymphoma malignant glioma myositis plasma cell myeloma subependymal giant cell astrocytoma thrombocytopenia due to immune destruction atypical teratoid rhabdoid tumor esophageal adenocarcinoma lung carcinoma mucopolysaccharidosis type 2 non-small cell lung carcinoma Relapse multiple myeloma
B	Pharos: P61769	familial visceral amyloidosis hypoproteinemia, hypercatabolic diffuse large B-cell lymphoma MHC class I deficiency esophageal squamous cell carcinoma kidney disease amyloidosis mature T-cell and NK-cell non-Hodgkin lymphoma autoimmune disease variant ABeta2M amyloidosis Hypergammaglobulinemia prostate cancer heart disease interstitial cystitis lung carcinoma familial visceral amyloidosis hypoproteinemia, hypercatabolic diffuse large B-cell lymphoma MHC class I deficiency esophageal squamous cell carcinoma kidney disease amyloidosis mature T-cell and NK-cell non-Hodgkin lymphoma autoimmune disease variant ABeta2M amyloidosis Hypergammaglobulinemia prostate cancer heart disease interstitial cystitis lung carcinoma ovarian cancer acquired metabolic disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia pilocytic astrocytoma psoriasis Sjogren syndrome glioblastoma juvenile dermatomyositis lung adenocarcinoma lymphatic system disease pancreatic intraductal papillary-mucinous carcinoma acute kidney failure periodic fever syndrome bone marrow disease rheumatoid arthritis Down syndrome subependymal giant cell astrocytoma lung cancer lymphoplasmacytic lymphoma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm cancer schizophrenia ulcerative colitis

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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.