1RZK

HIV-1 YU2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B

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 [auth G]	d1rzkg_	Alpha and beta proteins (a+b)	gp120 core	gp120 core	gp120 core	gp120 core	(Human immunodeficiency virus 1 ) [TaxId: 11676 ],	SCOPe (2.08)
B [auth C]	d1rzkc1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	CD4 V-set domains	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth C]	d1rzkc2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C2 set domains	CD4 C2-set domains	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth L]	d1rzkl1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	Immunoglobulin light chain kappa variable domain, VL-kappa	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth L]	d1rzkl2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	Immunoglobulin light chain kappa constant domain, CL-kappa	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth H]	d1rzkh1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	Immunoglobulin heavy chain variable domain, VH	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth H]	d1rzkh2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	Immunoglobulin heavy chain gamma constant domain 1, CH1-gamma	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)
B [auth C]	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8054739	3000071	SCOP2B (2022-06-29)
B [auth C]	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8054493	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 [auth G]	GP120_3rd	e1rzkG2	A: a+b two layers	X: Ribosomal protein L31e-like	H: Ribosomal protein L31e/gp120 outer domain (From Topology)	T: Ribosomal protein L31e/gp120 outer domain	F: GP120_3rd	ECOD (1.6)
A [auth G]	GP120_1st	e1rzkG1	A: a+b two layers	X: gp120 inner domain (From Topology)	H: gp120 inner domain (From Topology)	T: gp120 inner domain	F: GP120_1st	ECOD (1.6)
B [auth C]	C2-set	e1rzkC2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C2-set	ECOD (1.6)
B [auth C]	V-set_9	e1rzkC1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_9	ECOD (1.6)
C [auth L]	C1-set_4	e1rzkL2	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	e1rzkL1	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	e1rzkH1	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	e1rzkH2	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 [auth G]	2.170.40.20	Mainly Beta	Beta Complex	HIV Envelope Protein Gp120	Chain G	CATH (4.3.0)
B [auth C]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
D [auth H]	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 [auth C]	CD4	1V-1C-LIKE	Homo sapiens (human)	CD4	V-LIKE-DOMAIN V-LIKE, C-LIKE-DOMAIN C-LIKE	RPI	1V-1C-LIKE	IMGT (202445-0)
C [auth L]	17B mAb, anti-gp120 [HIV-1]	L-KAPPA	Homo sapiens (human)	IGKV3-1501, IGKV3D-1501, IGKJ201, IGKC01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202445-0)
D [auth H]	17B mAb, anti-gp120 [HIV-1]	VH-CH1	Homo sapiens (human)	IGHV1-6902, IGHV1-6904, IGHV1-6908, IGHV1-6909, IGHJ101, IGHG101, IGHG102, IGHG104, IGHG1*05	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202445-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
C [auth L]	Light Chain	IGKV3	Kappa	envelope glycoprotein gp120	SAbDab (2024-11-15)
D [auth H]	Heavy Chain	IGHV1	-	envelope glycoprotein gp120	SAbDab (2024-11-15)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B [auth C]	PF05790	Immunoglobulin C2-set domain (C2-set)	Immunoglobulin C2-set domain	-	Domain
B [auth C]	PF00047	Immunoglobulin domain (ig)	Immunoglobulin domain	Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-prot ...	Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth G]	ENVELOPE GLYCOPROTEIN GP120	structural molecule activity	viral process fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell membrane organization cellular component organization membrane fusion fusion of virus membrane with host plasma membrane cellular process cellular component organization or biogenesis regulation of establishment of T cell polarity regulation of establishment or maintenance of cell polarity multicellular organismal process establishment of lymphocyte polarity regulation of cellular process viral process fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell membrane organization cellular component organization membrane fusion fusion of virus membrane with host plasma membrane cellular process cellular component organization or biogenesis regulation of establishment of T cell polarity regulation of establishment or maintenance of cell polarity multicellular organismal process establishment of lymphocyte polarity regulation of cellular process regulation of leukocyte activation establishment of T cell polarity positive regulation of biological process regulation of cell activation positive regulation of leukocyte cell-cell adhesion establishment or maintenance of cell polarity lymphocyte activation leukocyte cell-cell adhesion leukocyte activation positive regulation of cell-cell adhesion positive regulation of lymphocyte activation positive regulation of cell activation cell adhesion cell-cell adhesion T cell activation positive regulation of establishment of T cell polarity positive regulation of leukocyte activation regulation of multicellular organismal process regulation of immune system process regulation of cell-cell adhesion positive regulation of immune system process positive regulation of cellular process regulation of biological process positive regulation of T cell activation positive regulation of cell adhesion regulation of cell adhesion cell activation biological regulation regulation of T cell activation establishment of cell polarity regulation of establishment of cell polarity immune system process regulation of leukocyte cell-cell adhesion positive regulation of multicellular organismal process regulation of lymphocyte activation protein localization regulation of localization cellular localization regulation of protein localization positive regulation of receptor clustering positive regulation of protein localization to membrane localization within membrane protein localization to membrane localization regulation of cellular localization cellular macromolecule localization macromolecule localization receptor clustering positive regulation of protein localization regulation of receptor clustering regulation of protein localization to membrane virion attachment to host cell biological process involved in interspecies interaction between organisms adhesion of symbiont to host cell viral life cycle adhesion of symbiont to host biological process involved in interaction with host biological process involved in symbiotic interaction symbiont-mediated perturbation of host defense response symbiont-mediated perturbation of host process modulation by virus of host process virus-mediated perturbation of host defense response modulation of process of another organism modulation by virus of host cellular process plasma membrane raft distribution regulation of cellular component organization positive regulation of cellular component organization plasma membrane raft polarization plasma membrane organization membrane raft organization endomembrane system organization membrane raft distribution plasma membrane raft localization membrane raft polarization regulation of plasma membrane raft polarization membrane raft localization regulation of plasma membrane organization positive regulation of plasma membrane raft polarization import into cell receptor-mediated endocytosis of virus by host cell transport establishment of localization vesicle-mediated transport symbiont entry into host cell clathrin-dependent endocytosis symbiont entry into host clathrin-dependent endocytosis of virus by host cell receptor-mediated endocytosis endocytosis endocytosis involved in viral entry into host cell transport of virus apoptotic process cell death programmed cell death viral gene expression viral protein processing	cellular anatomical structure membrane virion component virion membrane host intracellular membrane-bounded organelle host cellular component host intracellular part host cell membrane host cell cytoplasm part host intracellular organelle host cell endosome membrane host cell cytoplasm host cell part host cell endosome cellular anatomical structure membrane virion component virion membrane host intracellular membrane-bounded organelle host cellular component host intracellular part host cell membrane host cell cytoplasm part host intracellular organelle host cell endosome membrane host cell cytoplasm host cell part host cell endosome host intracellular region viral membrane viral envelope host cell plasma membrane
B [auth C]	T-CELL SURFACE GLYCOPROTEIN CD4	molecular transducer activity coreceptor activity signaling receptor activity protein-containing complex binding binding MHC protein complex binding MHC class II protein complex binding interleukin-16 binding protein binding cytokine binding protein tyrosine kinase binding kinase binding enzyme binding protein kinase binding molecular transducer activity coreceptor activity signaling receptor activity protein-containing complex binding binding MHC protein complex binding MHC class II protein complex binding interleukin-16 binding protein binding cytokine binding protein tyrosine kinase binding kinase binding enzyme binding protein kinase binding identical protein binding transmembrane signaling receptor activity virus receptor activity exogenous protein binding signaling receptor binding MHC class II protein binding MHC protein binding interleukin-16 receptor activity cytokine receptor activity immune receptor activity structural molecule activity extracellular matrix structural constituent protein homodimerization activity protein dimerization activity lipid binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcium-mediated signaling cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling signal transduction positive regulation of cellular process regulation of biological process regulation of signaling biological regulation positive regulation of intracellular signal transduction regulation of response to stimulus calcium-mediated signaling regulation of cell communication cellular process positive regulation of signaling maintenance of protein location protein localization localization cellular localization maintenance of protein location in cell cellular macromolecule localization macromolecule localization maintenance of location maintenance of location in cell immune response immune system process adaptive immune response regulation of calcium ion transport regulation of localization transport regulation of transport regulation of monoatomic ion transport establishment of localization metal ion transport calcium ion transport monoatomic ion transport regulation of metal ion transport monoatomic cation transport positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process positive regulation of metabolic process positive regulation of molecular function regulation of phosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process positive regulation of transferase activity positive regulation of phosphorus metabolic process phosphorylation positive regulation of catalytic activity regulation of molecular function positive regulation of kinase activity regulation of kinase activity regulation of phosphorylation regulation of phosphorus metabolic process metabolic process regulation of metabolic process developmental process multicellular organismal process cellular developmental process hemopoiesis cell activation cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell activation cell differentiation anatomical structure development T cell differentiation leukocyte differentiation interleukin-15-mediated signaling pathway cell surface receptor signaling pathway response to cytokine cellular response to interleukin-15 cytokine-mediated signaling pathway response to peptide response to chemical cellular response to cytokine stimulus response to interleukin-15 regulation of leukocyte activation regulation of cell activation regulation of T cell activation regulation of multicellular organismal process regulation of immune system process regulation of lymphocyte activation myeloid leukocyte differentiation regulation of leukocyte differentiation positive regulation of monocyte differentiation regulation of developmental process regulation of cell differentiation regulation of cell development positive regulation of developmental process multicellular organism development positive regulation of cell differentiation positive regulation of hemopoiesis monocyte differentiation positive regulation of immune system process regulation of multicellular organismal development regulation of monocyte differentiation regulation of myeloid cell differentiation positive regulation of cell development regulation of myeloid leukocyte differentiation positive regulation of myeloid leukocyte differentiation myeloid cell differentiation positive regulation of myeloid cell differentiation regulation of hemopoiesis positive regulation of multicellular organismal process positive regulation of leukocyte differentiation cell adhesion biological process involved in interspecies interaction between organisms response to other organism defense response response to external stimulus defense response to Gram-negative bacterium response to biotic stimulus defense response to bacterium defense response to other organism response to stress response to bacterium response to external biotic stimulus regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of primary metabolic process positive regulation of protein modification process positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein kinase activity protein modification process positive regulation of protein phosphorylation protein phosphorylation regulation of protein metabolic process primary metabolic process regulation of protein kinase activity regulation of macromolecule metabolic process macromolecule modification macromolecule metabolic process positive regulation of viral life cycle positive regulation of viral process viral life cycle modulation by symbiont of entry into host biological process involved in interaction with host biological process involved in symbiotic interaction regulation of viral entry into host cell regulation of viral life cycle regulation of viral process symbiont entry into host cell viral process symbiont entry into host positive regulation of viral entry into host cell positive regulation by symbiont of entry into host regulation of biological process involved in symbiotic interaction adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains helper T cell enhancement of adaptive immune response positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains regulation of adaptive immune response regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of immune response regulation of immune response positive regulation of adaptive immune response positive regulation of canonical NF-kappaB signal transduction canonical NF-kappaB signal transduction regulation of canonical NF-kappaB signal transduction 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 T cell selection response to granulocyte macrophage colony-stimulating factor cellular response to granulocyte macrophage colony-stimulating factor stimulus macrophage differentiation positive regulation of macromolecule biosynthetic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of biosynthetic process regulation of interleukin-2 production interleukin-2 production gene expression macromolecule biosynthetic process positive regulation of interleukin-2 production regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process positive regulation of cytokine production cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway positive regulation of DNA-templated transcription RNA metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process positive regulation of nucleobase-containing compound metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription 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-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 leukocyte cell-cell adhesion peptidyl-tyrosine modification positive regulation of peptidyl-tyrosine phosphorylation peptidyl-amino acid modification regulation of peptidyl-tyrosine phosphorylation peptidyl-tyrosine phosphorylation	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular organelle bounding membrane of organelle cytoplasmic vesicle vesicle membrane cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane membrane-bounded organelle intracellular anatomical structure intracellular vesicle intracellular organelle bounding membrane of organelle cytoplasmic vesicle vesicle membrane clathrin-coated vesicle endocytic vesicle membrane coated vesicle vesicle endocytic vesicle clathrin-coated vesicle membrane clathrin-coated endocytic vesicle membrane intracellular membrane-bounded organelle clathrin-coated endocytic vesicle cytoplasmic vesicle membrane coated vesicle membrane organelle cytoplasm organelle membrane membrane-enclosed lumen endomembrane system intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endoplasmic reticulum protein-containing complex plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex T cell receptor complex receptor complex membrane microdomain membrane raft organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum membrane early endosome endosome
C [auth L]	ANTIBODY 17B, LIGHT CHAIN	-	-	-
D [auth H]	ANTIBODY 17B, HEAVY CHAIN	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth G]	IPR000777	Human immunodeficiency virus 1, envelope glycoprotein Gp120	Domain
A [auth G]	IPR036377	Gp120 core superfamily	Homologous Superfamily
A [auth G]	IPR000328	Retroviral envelope protein GP41-like	Domain
A [auth G]	IPR037527	Envelope glycoprotein Gp160	Family
B [auth C]	IPR021963	T cell CD4 receptor C-terminal region	Domain
B [auth C]	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
B [auth C]	IPR013106	Immunoglobulin V-set domain	Domain
B [auth C]	IPR000973	T-cell surface antigen CD4	Family
B [auth C]	IPR003599	Immunoglobulin domain subtype	Domain
B [auth C]	IPR008424	Immunoglobulin C2-set	Domain
B [auth C]	IPR013151	Immunoglobulin-like beta-sandwich domain	Domain
B [auth C]	IPR015274	CD4, extracellular	Domain
B [auth C]	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
B [auth C]	IPR007110	Immunoglobulin-like domain	Domain
B [auth C]	IPR003598	Immunoglobulin subtype 2	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B [auth C]	Pharos: P01730	Duchenne muscular dystrophy diabetes mellitus AIDS-Related Opportunistic Infections lymphopenia coronary artery disease malignant glioma cryptococcosis neutropenia ovarian disease Duchenne and Becker muscular dystrophy pneumonia adult acute respiratory distress syndrome glioblastoma rheumatoid arthritis hepatitis B virus infection Duchenne muscular dystrophy diabetes mellitus AIDS-Related Opportunistic Infections lymphopenia coronary artery disease malignant glioma cryptococcosis neutropenia ovarian disease Duchenne and Becker muscular dystrophy pneumonia adult acute respiratory distress syndrome glioblastoma rheumatoid arthritis hepatitis B virus infection severe combined immunodeficiency arthritic joint disease HIV infectious disease IgA glomerulonephritis syphilis autoimmune disease influenza toxoplasmosis breast carcinoma kidney disease uveitis candidiasis lung carcinoma vertebral column disease colorectal cancer lymphoproliferative syndrome COVID-19 measles cutaneous lupus erythematosus obesity disorder diarrheal disease peripheral neuropathy prostate disease agammaglobulinemia heart disease rhinitis allergic disease hepatitis C virus infection hypereosinophilic syndrome skin disease asthma inborn carbohydrate metabolic disorder tetanus Becker muscular dystrophy interstitial lung disease tuberculosis breast disease leishmaniasis vaccinia colitis lymphatic system disease congenital T-cell immunodeficiency malaria Crohn disease demyelinating disease Okt4 epitope deficiency pneumocystosis encephalitis retinitis AIDS helminthiasis sarcoidosis anemia herpes zoster hypertensive disorder subependymal giant cell astrocytoma atherosclerosis infectious meningitis thrombocytopenia bone marrow disease invasive ductal breast carcinoma uterine disease cancer liver disease vasculitis colonic disease

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 R01GM157729.