3QI9

Crystal structure of mouse CD1d-alpha-phosphotidylinositol with mouse Valpha14-Vbeta6 2A3-D NKT TCR

External Resource: Annotation

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3qi9a2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	CD1, alpha-3 domain	Mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
A	d3qi9a1	Alpha and beta proteins (a+b)	MHC antigen-recognition domain	MHC antigen-recognition domain	MHC antigen-recognition domain	CD1, alpha-1 and alpha-2 domains	Mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
A	d3qi9a3	Artifacts	Tags	Tags	Tags	C-terminal Tags	Mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
B	d3qi9b_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	beta2-microglobulin	Mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
C	d3qi9c2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
C	d3qi9c1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
D	d3qi9d2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
D	d3qi9d1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	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	8054657	3000071	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	MHC antigen-recognition domain	8037146	3000521	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Immunoglobulin (Ig) domain-like	8054571	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	e3qi9A4	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	e3qi9A3	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	e3qi9B1	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	DUF1968	e3qi9C2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: DUF1968	ECOD (1.6)
C	V-set_4	e3qi9C1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_4	ECOD (1.6)
D	C1-set	e3qi9D3	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set	ECOD (1.6)
D	V-set_3	e3qi9D1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_3	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 (4.3.0)
A	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
D	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
A	CD1D1	I-ALPHA-LIKE	Mus musculus (house mouse)	-	-	RPI-MH1Like	MH1LIKE-ALPHA-LIKE_B2M	IMGT (202444-0)
B	CD1D1	B2M	Mus musculus (house mouse)	B2M*01	C-LIKE-DOMAIN C-LIKE	RPI-MH1Like	MH1LIKE-ALPHA-LIKE_B2M	IMGT (202444-0)
C	TR NKT TRAV1102-TRAJ1801, TRBV19*01	TR-ALPHA	Chimeric (chimeric)	TRAV1102, TRAJ1801, TRAC*01	V-DOMAIN V-ALPHA, C-DOMAIN C-ALPHA	TR	TR-ALPHA_BETA-2	IMGT (202444-0)
D	TR NKT TRAV1102-TRAJ1801, TRBV19*01	TR-BETA-2	Chimeric (chimeric)	TRBV1901, TRBJ1-101, TRBC201, TRBC202	V-DOMAIN V-BETA, C-DOMAIN C-BETA-2	TR	TR-ALPHA_BETA-2	IMGT (202444-0)

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	Antigen-presenting glycoprotein CD1d1	amide binding binding lipid binding lipopeptide binding protein-containing complex binding protein binding signaling receptor binding T cell receptor binding antigen binding exogenous lipid antigen binding lipid antigen binding endogenous lipid antigen binding	regulation of macrophage activation multicellular organismal process regulation of biological process positive regulation of macrophage activation regulation of cellular process regulation of leukocyte activation cell activation biological regulation positive regulation of biological process regulation of cell activation myeloid leukocyte activation leukocyte activation macrophage activation positive regulation of cell activation immune system process regulation of macrophage activation multicellular organismal process regulation of biological process positive regulation of macrophage activation regulation of cellular process regulation of leukocyte activation cell activation biological regulation positive regulation of biological process regulation of cell activation myeloid leukocyte activation leukocyte activation macrophage activation positive regulation of cell activation immune system process positive regulation of leukocyte activation positive regulation of multicellular organismal process cellular process regulation of multicellular organismal process regulation of immune system process positive regulation of immune system process positive regulation of cellular process response to stimulus immune response developmental process cellular developmental process hemopoiesis cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation alpha-beta T cell differentiation T cell activation cell differentiation anatomical structure development alpha-beta T cell activation NK T cell differentiation T cell differentiation leukocyte differentiation thymic T cell selection positive thymic T cell selection T cell differentiation in thymus positive T cell selection T cell selection biological process involved in interspecies interaction between organisms response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus defense response to other organism response to stress innate immune response response to external biotic stimulus regulation of response to stimulus regulation of immune response cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production positive regulation of macromolecule metabolic process regulation of biosynthetic process regulation of interleukin-2 production cellular metabolic process regulation of cellular metabolic process interleukin-2 production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of interleukin-2 production regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process positive regulation of cytokine production regulation of metabolic process positive regulation of cellular biosynthetic process regulation of leukocyte differentiation regulation of alpha-beta T cell activation regulation of cell differentiation positive regulation of T cell differentiation regulation of cell development positive regulation of developmental process multicellular organism development positive regulation of T cell activation positive regulation of cell development positive regulation of alpha-beta T cell activation regulation of leukocyte cell-cell adhesion positive regulation of alpha-beta T cell differentiation regulation of developmental process positive regulation of NK T cell differentiation positive regulation of leukocyte cell-cell adhesion regulation of alpha-beta T cell differentiation leukocyte cell-cell adhesion positive regulation of cell-cell adhesion regulation of T cell differentiation positive regulation of lymphocyte activation cell adhesion cell-cell adhesion positive regulation of hemopoiesis positive regulation of cell differentiation regulation of cell-cell adhesion regulation of lymphocyte differentiation regulation of multicellular organismal development positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation regulation of hemopoiesis positive regulation of leukocyte differentiation regulation of NK T cell differentiation positive regulation of lymphocyte differentiation regulation of lymphocyte activation antigen processing and presentation antigen processing and presentation of lipid antigen via MHC class Ib antigen processing and presentation via MHC class Ib antigen processing and presentation of endogenous antigen antigen processing and presentation, endogenous lipid antigen via MHC class Ib positive regulation of NK T cell activation regulation of NK T cell activation NK T cell activation antigen processing and presentation of exogenous antigen antigen processing and presentation, exogenous lipid antigen via MHC class Ib regulation of interleukin-4 production positive regulation of interleukin-4 production interleukin-4 production adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity regulation of immune effector process T cell mediated immunity positive regulation of leukocyte mediated immunity 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 response to stimulus regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of immune response positive regulation of leukocyte mediated cytotoxicity leukocyte mediated immunity positive regulation of immune effector process positive regulation of adaptive immune response regulation of T cell mediated immunity T cell mediated cytotoxicity positive regulation of T cell mediated cytotoxicity regulation of adaptive immune response regulation of leukocyte mediated cytotoxicity leukocyte mediated cytotoxicity adaptive immune response immune effector process regulation of leukocyte mediated immunity regulation of T cell mediated cytotoxicity regulation of lymphocyte mediated immunity positive regulation of T cell mediated immunity regulation of cell killing positive regulation of cell killing cell killing immature T cell proliferation in thymus leukocyte proliferation lymphocyte proliferation regulation of immature T cell proliferation T cell proliferation regulation of lymphocyte proliferation regulation of leukocyte proliferation cell population proliferation immature T cell proliferation regulation of immature T cell proliferation in thymus regulation of T cell proliferation regulation of cell population proliferation mononuclear cell proliferation regulation of mononuclear cell proliferation regulation of type II interferon production type II interferon production positive regulation of type II interferon production	cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle lytic vacuole vacuole cytoplasm cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle lytic vacuole vacuole cytoplasm intracellular membrane-bounded organelle lysosome early endosome endosome intracellular vesicle endomembrane system cytoplasmic vesicle vesicle vacuolar membrane lytic vacuole membrane bounding membrane of organelle lysosomal membrane organelle membrane endosome membrane cytoplasmic vesicle membrane vesicle membrane late endosome 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 cellular biosynthetic process cellular metabolic process primary 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 cellular biosynthetic process cellular metabolic process primary metabolic process gene expression macromolecule biosynthetic process protein maturation protein folding 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 iron(III) ion cellular response to metal ion response to iron(III) ion cellular response to iron ion cellular response to chemical stimulus response to metal ion response to iron ion response to chemical 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 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 defense response response to stress cellular defense response 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 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 supramolecular fiber organization amyloid fibril formation 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 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 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 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 protein-containing complex plasma membrane protein complex plasma membrane signaling receptor complex membrane protein complex HFE-transferrin receptor complex receptor complex intracellular anatomical structure cell periphery cell surface membrane plasma membrane cellular anatomical entity external side of plasma membrane side of membrane 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 membrane-bounded organelle 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 organelle late endosome vesicle 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 MHC class I peptide loading complex organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum protein-containing complex endoplasmic reticulum membrane extracellular region extracellular space MHC class II protein complex
C	NKT TCR V alpha 14	-	-	-
D	NKT TCR V beta 6 2A3-D	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
A	IPR050208	Antigen-presenting and immune regulatory MHC class I-related	Family
A	IPR003597	Immunoglobulin C1-set	Domain
A	IPR011161	MHC class I-like antigen recognition-like	Domain
A	IPR011162	MHC classes I/II-like antigen recognition protein	Homologous Superfamily
A	IPR037055	MHC class I-like antigen recognition-like superfamily	Homologous Superfamily
A	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A	IPR007110	Immunoglobulin-like domain	Domain
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	IPR050160	Major Histocompatibility Complex/Immunoglobulin	Family
B	IPR003597	Immunoglobulin C1-set	Domain
B	IPR015707	Beta-2-Microglobulin	Family

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.