4XT1

Structure of a nanobody-bound viral GPCR bound to human chemokine CX3CL1

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Membrane Protein Annotation: OPM
Membrane Protein Annotation: PDBTM
Membrane Protein Annotation: MemProtMD
Membrane Protein Annotation: mpstruc
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d4xt1b_	Alpha and beta proteins (a+b)	IL8-like	Interleukin 8-like chemokines	Interleukin 8-like chemokines	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d4xt1c1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	automated matches	(Vicugna pacos ) [TaxId: 30538 ],	SCOPe (2.08)
C	d4xt1c2	Artifacts	Tags	Tags	Tags	N-terminal Tags	(Vicugna pacos ) [TaxId: 30538 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Class A (rhodopsin) G protein-coupled receptor-like	8091231	4001858	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	G protein-coupled receptor-like	8091232	3000473	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Interleukin 8-like chemokines	8034324	3001955	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	7tm_1_1	e4xt1A1	A: alpha bundles	X: Family A G protein-coupled receptor-like (From Topology)	H: Family A G protein-coupled receptor-like (From Topology)	T: Family A G protein-coupled receptor-like	F: 7tm_1_1	ECOD (1.6)
B	IL8	e4xt1B1	A: beta barrels	X: IL8-related (From Homology)	H: IL8-related	T: IL8	F: IL8	ECOD (1.6)
C	V-set_8	e4xt1C1	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)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.1070.10	Mainly Alpha	Up-down Bundle	Rhopdopsin 7-helix transmembrane proteins	Rhodopsin 7-helix transmembrane proteins	CATH (4.3.0)
B	2.40.50.40	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)		CATH (4.3.0)
C	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
C	Heavy Chain	IGHV1	-	g-protein coupled receptor homolog us28	SAbDab (2024-04-19)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00001	7 transmembrane receptor (rhodopsin family) (7tm_1)	7 transmembrane receptor (rhodopsin family)	-	Family
B	PF00048	Small cytokines (intecrine/chemokine), interleukin-8 like (IL8)	Small cytokines (intecrine/chemokine), interleukin-8 like	Includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity. Structure contains two highly conserved disulfide bonds.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	G-protein coupled receptor homolog US28	G protein-coupled chemoattractant receptor activity molecular transducer activity chemokine receptor activity G protein-coupled receptor activity transmembrane signaling receptor activity signaling receptor activity cytokine receptor activity immune receptor activity	chemotaxis response to stimulus taxis response to chemical response to external stimulus locomotion regulation of biological process symbiont-mediated perturbation of host cellular process regulation of cellular process biological process involved in interspecies interaction between organisms positive regulation of cell division modulation by virus of host cell division biological regulation positive regulation of biological process chemotaxis response to stimulus taxis response to chemical response to external stimulus locomotion regulation of biological process symbiont-mediated perturbation of host cellular process regulation of cellular process biological process involved in interspecies interaction between organisms positive regulation of cell division modulation by virus of host cell division biological regulation positive regulation of biological process modulation by virus of host process biological process involved in interaction with host positive regulation by virus of host cell division regulation of cell division biological process involved in symbiotic interaction modulation by symbiont of host process viral process cellular process cell division modulation of process of another organism positive regulation of cellular process modulation by virus of host cellular process symbiont-mediated perturbation of host defense response response to host defenses response to other organism response to defenses of other organism virus-mediated perturbation of host defense response response to biotic stimulus response to host response to external biotic stimulus	membrane cellular anatomical entity host cell plasma membrane host cellular component host cell part host cell membrane
B	Fractalkine	CX3C chemokine receptor binding protein binding binding signaling receptor binding cytokine receptor binding G protein-coupled receptor binding chemokine receptor binding CCR chemokine receptor binding molecular function activator activity signaling receptor activator activity chemokine activity molecular function regulator activity cytokine activity signaling receptor regulator activity CX3C chemokine receptor binding protein binding binding signaling receptor binding cytokine receptor binding G protein-coupled receptor binding chemokine receptor binding CCR chemokine receptor binding molecular function activator activity signaling receptor activator activity chemokine activity molecular function regulator activity cytokine activity signaling receptor regulator activity receptor ligand activity CXCR1 chemokine receptor binding interleukin-8 receptor binding CXCR chemokine receptor binding cell adhesion molecule binding protein-containing complex binding integrin binding chemoattractant activity	cellular response to stimulus response to organic substance regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication cellular response to chemical stimulus response to chemical cellular response to cytokine stimulus cellular response to stimulus response to organic substance regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication cellular response to chemical stimulus response to chemical cellular response to cytokine stimulus cellular process cellular response to organic substance signal transduction developmental process multicellular organismal process regulation of multicellular organismal development regulation of developmental process cellular developmental process cell development regulation of neurogenesis regulation of cell differentiation nervous system development regulation of cell development regulation of nervous system development multicellular organism development neurogenesis cell differentiation anatomical structure development regulation of multicellular organismal process system development regulation of tumor necrosis factor production cellular biosynthetic process negative regulation of biological process negative regulation of cellular metabolic process negative regulation of tumor necrosis factor production organic substance metabolic process cytokine production organic substance biosynthetic process regulation of cytokine production negative regulation of cellular process negative regulation of macromolecule metabolic process regulation of biosynthetic process cellular metabolic process negative regulation of metabolic process tumor necrosis factor superfamily cytokine production regulation of cellular metabolic process negative regulation of cytokine production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process tumor necrosis factor production negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression regulation of tumor necrosis factor superfamily cytokine production biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of tumor necrosis factor superfamily cytokine production metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process negative regulation of multicellular organismal process regulation of metabolic process regulation of defense response regulation of response to external stimulus defense response positive regulation of biological process 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 positive regulation of locomotion regulation of cell motility regulation of microglial cell migration glial cell migration macrophage migration regulation of glial cell migration positive regulation of cell migration regulation of macrophage migration gliogenesis positive regulation of cell motility regulation of cell migration myeloid leukocyte migration positive regulation of mononuclear cell migration positive regulation of microglial cell migration cell migration regulation of immune system process regulation of mononuclear cell migration cell motility positive regulation of immune system process locomotion positive regulation of cellular process positive regulation of macrophage migration regulation of leukocyte migration microglial cell migration positive regulation of leukocyte migration leukocyte migration positive regulation of glial cell migration immune system process regulation of locomotion mononuclear cell migration cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein-containing complex assembly integrin activation cellular component organization or biogenesis interleukin-6 production regulation of interleukin-6 production negative regulation of interleukin-6 production developmental maturation generation of neurons neuron differentiation neuron remodeling anatomical structure maturation neuron development neuron maturation cell maturation regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion cell-substrate adhesion positive regulation of cell-matrix adhesion cell adhesion cell-matrix adhesion positive regulation of cell-substrate adhesion regulation of cell-matrix adhesion response to ischemia cell chemotaxis chemotaxis neutrophil chemotaxis neutrophil migration granulocyte migration taxis granulocyte chemotaxis leukocyte chemotaxis cell-cell signaling positive chemotaxis leukocyte migration involved in inflammatory response autocrine signaling regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization cell projection organization neuron projection development positive regulation of neuron projection development positive regulation of cell projection organization plasma membrane bounded cell projection organization regulation of cell projection organization regulation of plasma membrane bounded cell projection organization signal transduction in absence of ligand cell death extrinsic apoptotic signaling pathway apoptotic signaling pathway extrinsic apoptotic signaling pathway in absence of ligand apoptotic process programmed cell death negative regulation of locomotion negative regulation of cell motility negative regulation of cell migration cell population proliferation regulation of smooth muscle cell proliferation positive regulation of cell population proliferation smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation regulation of cell population proliferation muscle cell proliferation eosinophil chemotaxis eosinophil migration positive regulation of phosphorylation positive regulation of phosphate metabolic process intracellular signal transduction regulation of primary metabolic process positive regulation of metabolic process regulation of phosphate metabolic process intracellular signaling cassette phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process protein modification process phosphorus metabolic process positive regulation of protein phosphorylation I-kappaB phosphorylation protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process macromolecule modification regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of cellular metabolic process positive regulation of protein modification process positive regulation of I-kappaB phosphorylation protein metabolic process organonitrogen compound metabolic process canonical NF-kappaB signal transduction regulation of phosphorylation regulation of I-kappaB phosphorylation lymphocyte chemotaxis lymphocyte migration wound healing blood vessel morphogenesis tube development angiogenesis involved in wound healing angiogenesis vasculature development circulatory system development anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis response to wounding blood vessel development positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of biosynthetic process regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process cellular response to interleukin-1 response to interleukin-1 cell activation myeloid leukocyte activation leukocyte activation macrophage activation leukocyte activation involved in inflammatory response microglial cell activation glial cell activation neuroinflammatory response cellular homeostasis neuron cellular homeostasis homeostatic process positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction regulation of signal transduction regulation of intracellular signal transduction regulation of signaling positive regulation of intracellular signal transduction regulation of cell communication regulation of canonical NF-kappaB signal transduction positive regulation of signaling negative regulation of extrinsic apoptotic signaling pathway in absence of ligand negative regulation of signaling regulation of programmed cell death negative regulation of cell communication negative regulation of signal transduction in absence of ligand negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway negative regulation of response to stimulus negative regulation of programmed cell death regulation of apoptotic process negative regulation of signal transduction regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic process regulation of extrinsic apoptotic signaling pathway in absence of ligand regulation of apoptotic signaling pathway positive regulation of ERK1 and ERK2 cascade positive regulation of MAPK cascade regulation of MAPK cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade immune response regulation of macrophage activation negative regulation of inflammatory response regulation of leukocyte activation regulation of cell activation regulation of neuroinflammatory response negative regulation of microglial cell activation negative regulation of cell activation negative regulation of immune system process negative regulation of response to external stimulus negative regulation of defense response regulation of microglial cell activation negative regulation of neuroinflammatory response negative regulation of leukocyte activation negative regulation of macrophage activation regulation of transforming growth factor beta production transforming growth factor beta1 production regulation of transforming growth factor beta1 production positive regulation of transforming growth factor beta1 production transforming growth factor beta production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of transforming growth factor beta production positive regulation of cytokine production response to chemokine cellular response to chemokine chemokine-mediated signaling pathway G protein-coupled receptor signaling pathway interleukin-1 production regulation of interleukin-1 beta production negative regulation of interleukin-1 beta production negative regulation of interleukin-1 production regulation of interleukin-1 production interleukin-1 beta production regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of lipopolysaccharide-mediated signaling pathway regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms response to lipid cellular response to lipopolysaccharide response to biotic stimulus lipopolysaccharide-mediated signaling pathway cellular response to biotic stimulus response to bacterium response to external biotic stimulus response to other organism response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to lipid response to molecule of bacterial origin negative regulation of interleukin-1 alpha production regulation of interleukin-1 alpha production interleukin-1 alpha production cellular component disassembly cell junction organization cell junction disassembly synapse pruning synapse organization cellular response to tumor necrosis factor response to tumor necrosis factor positive regulation of organelle organization regulation of cytoskeleton organization regulation of actin filament-based process regulation of actin filament bundle assembly positive regulation of actin filament bundle assembly actin filament bundle organization actin filament-based process regulation of actin filament organization actin cytoskeleton organization positive regulation of cellular component biogenesis positive regulation of cytoskeleton organization actin filament organization positive regulation of supramolecular fiber organization regulation of cellular component biogenesis regulation of organelle organization organelle organization actin filament bundle assembly regulation of actin cytoskeleton organization regulation of supramolecular fiber organization supramolecular fiber organization cytoskeleton organization response to type II interferon cellular response to type II interferon innate immune response defense response to symbiont defense response to other organism monocyte chemotaxis leukocyte adhesive activation cellular extravasation regulation of calcium-independent cell-cell adhesion positive regulation of cell-cell adhesion cell-cell adhesion calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules regulation of cell-cell adhesion cell-cell adhesion via plasma-membrane adhesion molecules positive regulation of calcium-independent cell-cell adhesion negative regulation of cell adhesion negative regulation of cell-substrate adhesion regulation of synaptic plasticity trans-synaptic signaling modulation of chemical synaptic transmission chemical synaptic transmission synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of biological quality microglial cell proliferation leukocyte proliferation macrophage proliferation glial cell proliferation regulation of calcium ion transport regulation of localization positive regulation of cation transmembrane transport positive regulation of calcium ion transport intracellular calcium ion homeostasis calcium ion transport localization positive regulation of monoatomic ion transport positive regulation of monoatomic ion transmembrane transport monoatomic cation homeostasis monoatomic cation transport intracellular monoatomic ion homeostasis regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol regulation of transmembrane transport chemical homeostasis cellular localization inorganic ion homeostasis transport monoatomic ion transmembrane transport calcium ion homeostasis regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion metal ion transport maintenance of location in cell regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport intracellular monoatomic cation homeostasis monoatomic ion homeostasis positive regulation of calcium ion transmembrane transport positive regulation of transmembrane transport monoatomic ion transport intracellular chemical homeostasis positive regulation of release of sequestered calcium ion into cytosol regulation of metal ion transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol regulation of transport sequestering of calcium ion positive regulation of transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport negative regulation of neuron migration regulation of neuron migration neuron migration glutamate receptor signaling pathway negative regulation of glutamate receptor signaling pathway regulation of glutamate receptor signaling pathway neuron apoptotic process negative regulation of neuron apoptotic process hippocampal neuron apoptotic process regulation of hippocampal neuron apoptotic process negative regulation of hippocampal neuron apoptotic process regulation of neuron apoptotic process neuroblast proliferation positive regulation of nervous system development regulation of neuroblast proliferation positive regulation of developmental process positive regulation of cell differentiation positive regulation of neurogenesis regulation of neural precursor cell proliferation positive regulation of cell development positive regulation of neural precursor cell proliferation positive regulation of neuroblast proliferation neural precursor cell proliferation	membrane cellular anatomical entity cell projection neuron projection plasma membrane bounded cell projection intracellular anatomical structure perinuclear region of cytoplasm cytoplasm somatodendritic compartment cell body neuronal cell body extracellular region extracellular space cell surface membrane cellular anatomical entity cell projection neuron projection plasma membrane bounded cell projection intracellular anatomical structure perinuclear region of cytoplasm cytoplasm somatodendritic compartment cell body neuronal cell body extracellular region extracellular space cell surface cell periphery plasma membrane
C	nanobody 7	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR000355	Chemokine receptor family	Family
A	IPR000276	G protein-coupled receptor, rhodopsin-like	Family
A	IPR017452	GPCR, rhodopsin-like, 7TM	Domain
B	IPR001811	Chemokine interleukin-8-like domain	Domain
B	IPR034127	CX3C chemokine domain	Domain
B	IPR036048	Chemokine interleukin-8-like superfamily	Homologous Superfamily
B	IPR039809	Chemokine beta/gamma/delta	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: P78423	allergic disease Diabetes Mellitus, Experimental pneumonia prostate cancer ovarian cancer pneumonitis transitional cell carcinoma breast cancer lung carcinoma medulloblastoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia primitive neuroectodermal tumor breast carcinoma invasive ductal breast carcinoma lung adenocarcinoma allergic disease Diabetes Mellitus, Experimental pneumonia prostate cancer ovarian cancer pneumonitis transitional cell carcinoma breast cancer lung carcinoma medulloblastoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia primitive neuroectodermal tumor breast carcinoma invasive ductal breast carcinoma lung adenocarcinoma malignant ependymoma myocardial ischemia systemic lupus erythematosus atypical teratoid rhabdoid tumor coronary artery disease glioblastoma large cell medulloblastoma lung cancer malignant glioma

Membrane Protein Annotation: OPM OPM Database Homepage

Chains	External Link	Type	Class	Superfamily	Family
A, B	OPM	Transmembrane	Alpha-helical polytopic	Rhodopsin-like receptors and pumps	G-protein coupled receptors, family A

Membrane Protein Annotation: PDBTM PDBTM Database Homepage

Chains	External Link	Comment
A, B	PDBTM	Annotated as membrane protein by PDBTM

Membrane Protein Annotation: MemProtMD MemProtMD Database Homepage

Chains	External Link	Comment
A, B	MemProtMD	Annotated as membrane protein by MemProtMD

Membrane Protein Annotation: mpstruc mpstruc Database Homepage

Chains	Resource Link	Group	Subgroup	Protein
A, B	mpstruc	TRANSMEMBRANE PROTEINS: ALPHA-HELICAL	G Protein-Coupled Receptors: Class A	Human cytomeglovirius US28 GPCR with bound human cytokine CX3CL1

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B	PCA	Parent Component: GLN RESID: AA0031 PSI-MOD : 2-pyrrolidone-5-carboxylic acid (Gln) MOD:00040 , 2-pyrrolidone-5-carboxylic acid (Glu) MOD:00420