Annotations: 2BA1

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
G [auth H]	d2ba1h1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	Ribonuclease PH domain 1-like	Exosome complex exonuclease 2,ECX2	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
G [auth H]	d2ba1h2	Alpha and beta proteins (a+b)	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Exosome complex exonuclease 2, ECX2	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
H [auth G]	d2ba1g1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	Ribonuclease PH domain 1-like	Exosome complex exonuclease 2,ECX2	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
H [auth G]	d2ba1g2	Alpha and beta proteins (a+b)	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Exosome complex exonuclease 2, ECX2	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
I	d2ba1i1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	Ribonuclease PH domain 1-like	Exosome complex exonuclease 2,ECX2	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
I	d2ba1i2	Alpha and beta proteins (a+b)	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Exosome complex exonuclease 2, ECX2	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
D [auth E]	d2ba1e1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	Ribonuclease PH domain 1-like	Exosome complex exonuclease 1, ECX1	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
D [auth E]	d2ba1e2	Alpha and beta proteins (a+b)	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Exosome complex exonuclease 1, ECX1	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
E [auth D]	d2ba1d1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	Ribonuclease PH domain 1-like	Exosome complex exonuclease 1, ECX1	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
E [auth D]	d2ba1d2	Alpha and beta proteins (a+b)	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Exosome complex exonuclease 1, ECX1	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
F	d2ba1f1	Alpha and beta proteins (a+b)	Ribosomal protein S5 domain 2-like	Ribosomal protein S5 domain 2-like	Ribonuclease PH domain 1-like	Exosome complex exonuclease 1, ECX1	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)
F	d2ba1f2	Alpha and beta proteins (a+b)	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Ribonuclease PH domain 2-like	Exosome complex exonuclease 1, ECX1	(Archaeoglobus fulgidus ) [TaxId: 2234 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
G [auth H]	SCOP2B Superfamily	Ribosomal protein S5 domain 2-like	8033526	3000100	SCOP2B (2022-06-29)
G [auth H]	SCOP2B Superfamily	Ribonuclease PH domain 2-like	8033527	3000346	SCOP2B (2022-06-29)
H [auth G]	SCOP2B Superfamily	Ribonuclease PH domain 2-like	8033527	3000346	SCOP2B (2022-06-29)
H [auth G]	SCOP2B Superfamily	Ribosomal protein S5 domain 2-like	8033526	3000100	SCOP2B (2022-06-29)
I	SCOP2B Superfamily	Ribonuclease PH domain 2-like	8033527	3000346	SCOP2B (2022-06-29)
I	SCOP2B Superfamily	Ribosomal protein S5 domain 2-like	8033526	3000100	SCOP2B (2022-06-29)
D [auth E]	SCOP2B Superfamily	Ribosomal protein S5 domain 2-like	8033518	3000100	SCOP2B (2022-06-29)
D [auth E]	SCOP2B Superfamily	Ribonuclease PH domain 2-like	8033521	3000346	SCOP2B (2022-06-29)
E [auth D]	SCOP2B Superfamily	Ribosomal protein S5 domain 2-like	8033518	3000100	SCOP2B (2022-06-29)
E [auth D]	SCOP2B Superfamily	Ribonuclease PH domain 2-like	8033521	3000346	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Ribonuclease PH domain 2-like	8033521	3000346	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Ribosomal protein S5 domain 2-like	8033518	3000100	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)
G [auth H]	PF01138	e2ba1H2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: PF01138	ECOD (1.6)
G [auth H]	PF03725	e2ba1H1	A: a+b two layers	X: Ribonuclease PH domain 2-like	H: Ribonuclease PH domain 2 (From Topology)	T: Ribonuclease PH domain 2	F: PF03725	ECOD (1.6)
H [auth G]	PF01138	e2ba1G2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: PF01138	ECOD (1.6)
H [auth G]	PF03725	e2ba1G1	A: a+b two layers	X: Ribonuclease PH domain 2-like	H: Ribonuclease PH domain 2 (From Topology)	T: Ribonuclease PH domain 2	F: PF03725	ECOD (1.6)
I	PF01138	e2ba1I2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: PF01138	ECOD (1.6)
I	PF03725	e2ba1I1	A: a+b two layers	X: Ribonuclease PH domain 2-like	H: Ribonuclease PH domain 2 (From Topology)	T: Ribonuclease PH domain 2	F: PF03725	ECOD (1.6)
A	PF10447	e2ba1A1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF10447	ECOD (1.6)
A	PF14382	e2ba1A2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Ribosomal L27 protein	F: PF14382	ECOD (1.6)
B [auth C]	PF10447	e2ba1C1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF10447	ECOD (1.6)
B [auth C]	PF14382	e2ba1C2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Ribosomal L27 protein	F: PF14382	ECOD (1.6)
C [auth B]	PF10447	e2ba1B1	A: beta barrels	X: OB-fold	H: Nucleic acid-binding proteins (From Topology)	T: Nucleic acid-binding proteins	F: PF10447	ECOD (1.6)
C [auth B]	PF14382	e2ba1B2	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Ribosomal L27 protein	F: PF14382	ECOD (1.6)
D [auth E]	PF01138	e2ba1E2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: PF01138	ECOD (1.6)
D [auth E]	PF03725	e2ba1E1	A: a+b two layers	X: Ribonuclease PH domain 2-like	H: Ribonuclease PH domain 2 (From Topology)	T: Ribonuclease PH domain 2	F: PF03725	ECOD (1.6)
E [auth D]	PF01138	e2ba1D2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: PF01138	ECOD (1.6)
E [auth D]	PF03725	e2ba1D1	A: a+b two layers	X: Ribonuclease PH domain 2-like	H: Ribonuclease PH domain 2 (From Topology)	T: Ribonuclease PH domain 2	F: PF03725	ECOD (1.6)
F	PF01138	e2ba1F2	A: a+b two layers	X: Ribosomal protein S5 domain 2-like (From Topology)	H: Ribosomal protein S5 domain 2-like (From Topology)	T: Ribosomal protein S5 domain 2-like	F: PF01138	ECOD (1.6)
F	PF03725	e2ba1F1	A: a+b two layers	X: Ribonuclease PH domain 2-like	H: Ribonuclease PH domain 2 (From Topology)	T: Ribonuclease PH domain 2	F: PF03725	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
G [auth H]	3.30.230.70	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
H [auth G]	3.30.230.70	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
I	3.30.230.70	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
A	2.40.50.100	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	RNA polymerase II/Efflux pump adaptor protein, barrel-sandwich hybrid domain	CATH (4.3.0)
A	2.40.50.140	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	Nucleic acid-binding proteins	CATH (4.3.0)
A	2.20.70.10	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
B [auth C]	2.40.50.100	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	RNA polymerase II/Efflux pump adaptor protein, barrel-sandwich hybrid domain	CATH (4.3.0)
B [auth C]	2.40.50.140	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	Nucleic acid-binding proteins	CATH (4.3.0)
B [auth C]	2.20.70.10	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
C [auth B]	2.40.50.100	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	RNA polymerase II/Efflux pump adaptor protein, barrel-sandwich hybrid domain	CATH (4.3.0)
C [auth B]	2.40.50.140	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	Nucleic acid-binding proteins	CATH (4.3.0)
C [auth B]	2.20.70.10	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
D [auth E]	3.30.230.70	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
E [auth D]	3.30.230.70	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)
F	3.30.230.70	Alpha Beta	2-Layer Sandwich	Ribosomal Protein S5	domain 2	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
G [auth H], H [auth G], I	PF03725	3' exoribonuclease family, domain 2 (RNase_PH_C)	3' exoribonuclease family, domain 2	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of ...	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of the domain. PNPase is involved in mRNA degradation in a 3'-5' direction. The exosome is a 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA. Three of its five protein components, Swiss:P46948 Swiss:Q12277 and Swiss:P25359 contain a copy of this domain [1]. Swiss:Q10205, a hypothetical protein from S. pombe appears to belong to an uncharacterised subfamily. This subfamily is found in both eukaryotes and archaebacteria.	Domain
G [auth H], H [auth G], I	PF01138	3' exoribonuclease family, domain 1 (RNase_PH)	3' exoribonuclease family, domain 1	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of ...	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of the domain. PNPase is involved in mRNA degradation in a 3'-5' direction. The exosome is a 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA. Three of its five protein components, Swiss:P46948 Swiss:Q12277 and Swiss:P25359 contain a copy of this domain [1]. Swiss:Q10205, a hypothetical protein from S. pombe appears to belong to an uncharacterised subfamily. This subfamily is found in both eukaryotes and archaebacteria.	Domain
A, B [auth C], C [auth B]	PF14382	Exosome complex exonuclease RRP4 N-terminal region (ECR1_N)	Exosome complex exonuclease RRP4 N-terminal region	ECR1_N is an N-terminal region of the exosome complex exonuclease RRP proteins. It is a G-rich domain which structurally is a rudimentary single hybrid fold with a permuted topology.	Domain
A, B [auth C], C [auth B]	PF10447	Exosome component EXOSC1/CSL4 (EXOSC1)	Exosome component EXOSC1/CSL4	This family of proteins are components of the exosome 3'->5' exoribonuclease complex. The exosome mediates degradation of unstable mRNAs that contain AU-rich elements (AREs) within their 3' untranslated regions [1].	Domain
D [auth E], E [auth D], F	PF03725	3' exoribonuclease family, domain 2 (RNase_PH_C)	3' exoribonuclease family, domain 2	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of ...	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of the domain. PNPase is involved in mRNA degradation in a 3'-5' direction. The exosome is a 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA. Three of its five protein components, Swiss:P46948 Swiss:Q12277 and Swiss:P25359 contain a copy of this domain [1]. Swiss:Q10205, a hypothetical protein from S. pombe appears to belong to an uncharacterised subfamily. This subfamily is found in both eukaryotes and archaebacteria.	Domain
D [auth E], E [auth D], F	PF01138	3' exoribonuclease family, domain 1 (RNase_PH)	3' exoribonuclease family, domain 1	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of ...	This family includes 3'-5' exoribonucleases. Ribonuclease PH contains a single copy of this domain, and removes nucleotide residues following the -CCA terminus of tRNA. Polyribonucleotide nucleotidyltransferase (PNPase) contains two tandem copies of the domain. PNPase is involved in mRNA degradation in a 3'-5' direction. The exosome is a 3'-5' exoribonuclease complex that is required for 3' processing of the 5.8S rRNA. Three of its five protein components, Swiss:P46948 Swiss:Q12277 and Swiss:P25359 contain a copy of this domain [1]. Swiss:Q10205, a hypothetical protein from S. pombe appears to belong to an uncharacterised subfamily. This subfamily is found in both eukaryotes and archaebacteria.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
G [auth H], H [auth G], I	Archaeal exosome complex exonuclease RRP42	-	catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process organic substance catabolic process catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process organic substance catabolic process RNA catabolic process	exosome (RNase complex) protein-containing complex intracellular anatomical structure catalytic complex cellular anatomical entity exoribonuclease complex cytoplasm
A, B [auth C], C [auth B]	Archaeal exosome RNA binding protein CSL4	cation binding transition metal ion binding zinc ion binding ion binding binding metal ion binding small molecule binding RNA binding organic cyclic compound binding nucleic acid binding	catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process organic substance catabolic process catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process organic substance catabolic process RNA catabolic process cellular biosynthetic process cellular metabolic process gene expression macromolecule biosynthetic process biosynthetic process organic substance biosynthetic process cellular process RNA processing	exosome (RNase complex) protein-containing complex intracellular anatomical structure catalytic complex cellular anatomical entity exoribonuclease complex cytoplasm
D [auth E], E [auth D], F	Archaeal exosome complex exonuclease RRP41	3'-5'-RNA exonuclease activity catalytic activity, acting on RNA RNA exonuclease activity, producing 5'-phosphomonoesters catalytic activity, acting on a nucleic acid 3'-5' exonuclease activity RNA exonuclease activity RNA nuclease activity hydrolase activity exonuclease activity, active with either ribo- or deoxyribonucleic acids and producing 5'-phosphomonoesters nuclease activity hydrolase activity, acting on ester bonds exonuclease activity catalytic activity	catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process organic substance catabolic process catabolic process RNA metabolic process primary metabolic process nucleic acid metabolic process macromolecule catabolic process organic cyclic compound catabolic process nucleobase-containing compound catabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process nucleic acid catabolic process metabolic process macromolecule metabolic process organic substance catabolic process RNA catabolic process	exosome (RNase complex) protein-containing complex intracellular anatomical structure catalytic complex cellular anatomical entity exoribonuclease complex cytoplasm

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
G [auth H], H [auth G], I	IPR027408	PNPase/RNase PH domain superfamily	Homologous Superfamily
G [auth H], H [auth G], I	IPR001247	Exoribonuclease, phosphorolytic domain 1	Domain
G [auth H], H [auth G], I	IPR036345	Exoribonuclease, PH domain 2 superfamily	Homologous Superfamily
G [auth H], H [auth G], I	IPR020568	Ribosomal protein uS5 domain 2-type superfamily	Homologous Superfamily
G [auth H], H [auth G], I	IPR015847	Exoribonuclease, phosphorolytic domain 2	Domain
G [auth H], H [auth G], I	IPR020869	Exosome complex component Rrp42, archaea	Family
A, B [auth C], C [auth B]	IPR030850	Exosome complex component Csl4, archaea	Family
A, B [auth C], C [auth B]	IPR039771	Exosome complex component Csl4	Family
A, B [auth C], C [auth B]	IPR003029	S1 domain	Domain
A, B [auth C], C [auth B]	IPR025721	Exosome complex component, N-terminal domain	Domain
A, B [auth C], C [auth B]	IPR012340	Nucleic acid-binding, OB-fold	Homologous Superfamily
A, B [auth C], C [auth B]	IPR019495	Exosome complex component CSL4, C-terminal	Domain
D [auth E], E [auth D], F	IPR011807	Exosome complex component Rrp41	Family
D [auth E], E [auth D], F	IPR027408	PNPase/RNase PH domain superfamily	Homologous Superfamily
D [auth E], E [auth D], F	IPR001247	Exoribonuclease, phosphorolytic domain 1	Domain
D [auth E], E [auth D], F	IPR036345	Exoribonuclease, PH domain 2 superfamily	Homologous Superfamily
D [auth E], E [auth D], F	IPR020568	Ribosomal protein uS5 domain 2-type superfamily	Homologous Superfamily
D [auth E], E [auth D], F	IPR015847	Exoribonuclease, phosphorolytic domain 2	Domain

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.