BFRB_MYCTU
ID BFRB_MYCTU Reviewed; 181 AA.
AC P9WNE5; L0TGW6; P96237; Q7BS08; Q7D4R7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Bacterioferritin BfrB {ECO:0000303|PubMed:9634230};
DE EC=1.16.3.1 {ECO:0000269|PubMed:21494619, ECO:0000269|Ref.12};
DE AltName: Full=Non-heme ferritin Ftn {ECO:0000303|PubMed:9864257};
DE AltName: Full=Nox19 {ECO:0000303|PubMed:9864257};
GN Name=bfrB {ECO:0000303|PubMed:9864257}; Synonyms=ftn;
GN OrderedLocusNames=Rv3841;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-17, AND INDUCTION
RP BY NITRIC OXIDE STRESS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9864257; DOI=10.1128/iai.67.1.460-465.1999;
RA Garbe T.R., Hibler N.S., Deretic V.;
RT "Response to reactive nitrogen intermediates in Mycobacterium tuberculosis:
RT induction of the 16-kilodalton alpha-crystallin homolog by exposure to
RT nitric oxide donors.";
RL Infect. Immun. 67:460-465(1999).
RN [3]
RP INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11416222; DOI=10.1073/pnas.121172498;
RA Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I.,
RA Schoolnik G.K.;
RT "Regulation of the Mycobacterium tuberculosis hypoxic response gene
RT encoding alpha -crystallin.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12057942; DOI=10.1128/jb.184.13.3485-3491.2002;
RA Rosenkrands I., Slayden R.A., Crawford J., Aagaard C., Barry C.E. III,
RA Andersen P.;
RT "Hypoxic response of Mycobacterium tuberculosis studied by metabolic
RT labeling and proteome analysis of cellular and extracellular proteins.";
RL J. Bacteriol. 184:3485-3491(2002).
RN [5]
RP INDUCED BY IRON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12065475; DOI=10.1128/iai.70.7.3371-3381.2002;
RA Rodriguez G.M., Voskuil M.I., Gold B., Schoolnik G.K., Smith I.;
RT "IdeR, an essential gene in Mycobacterium tuberculosis: role of IdeR in
RT iron-dependent gene expression, iron metabolism, and oxidative stress
RT response.";
RL Infect. Immun. 70:3371-3381(2002).
RN [6]
RP REPRESSION BY CARBON MONOXIDE (CO).
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007;
RA Shiloh M.U., Manzanillo P., Cox J.S.;
RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during
RT macrophage infection.";
RL Cell Host Microbe 3:323-330(2008).
RN [7]
RP CRYSTALLIZATION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21139218; DOI=10.1107/s1744309110042958;
RA McMath L.M., Habel J.E., Sankaran B., Yu M., Hung L.W., Goulding C.W.;
RT "Crystallization and preliminary X-ray crystallographic analysis of a
RT Mycobacterium tuberculosis ferritin homolog, BfrB.";
RL Acta Crystallogr. F 66:1657-1661(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [9]
RP DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=22101841; DOI=10.1128/jb.05553-11;
RA Reddy P.V., Puri R.V., Khera A., Tyagi A.K.;
RT "Iron storage proteins are essential for the survival and pathogenesis of
RT Mycobacterium tuberculosis in THP-1 macrophages and the guinea pig model of
RT infection.";
RL J. Bacteriol. 194:567-575(2012).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS
RP OF 167-ALA--LEU-181.
RC STRAIN=H37Rv;
RX PubMed=24855650; DOI=10.1074/jbc.m114.570119;
RA Contreras H., Joens M.S., McMath L.M., Le V.P., Tullius M.V., Kimmey J.M.,
RA Bionghi N., Horwitz M.A., Fitzpatrick J.A., Goulding C.W.;
RT "Characterization of a Mycobacterium tuberculosis nanocompartment and its
RT potential cargo proteins.";
RL J. Biol. Chem. 289:18279-18289(2014).
RN [11] {ECO:0007744|PDB:3QD8}
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, AND MUTAGENESIS OF 168-PRO--LEU-181.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21494619; DOI=10.1371/journal.pone.0018570;
RA Khare G., Gupta V., Nangpal P., Gupta R.K., Sauter N.K., Tyagi A.K.;
RT "Ferritin structure from Mycobacterium tuberculosis: comparative study with
RT homologues identifies extended C-terminus involved in ferroxidase
RT activity.";
RL PLoS ONE 6:E18570-E18570(2011).
RN [12] {ECO:0007744|PDB:3UNO}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS).
RA McMath L.M., Contreras H., Goulding C.W.;
RT "Mycobacterium tuberculosis ferritin homolog, BfrB.";
RL Submitted (NOV-2011) to the PDB data bank.
RN [13] {ECO:0007744|PDB:7O6E}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.10 ANGSTROMS), SUBUNIT, AND
RP BIOTECHNOLOGY.
RX PubMed=34342280; DOI=10.1107/s2059798321007233;
RA Gijsbers A., Zhang Y., Gao Y., Peters P.J., Ravelli R.B.G.;
RT "Mycobacterium tuberculosis ferritin: a suitable workhorse protein for
RT cryo-EM development.";
RL Acta Crystallogr. D 77:1077-1083(2021).
CC -!- FUNCTION: Possible cargo protein of a type 1 encapsulin nanocompartment
CC involved in protection against oxidative stress (Probable). Iron-
CC storage protein that displays ferroxidase activity, catalyzing the
CC oxidation of Fe(2+) ions into Fe(3+) ions, that can then be deposited
CC as a ferric-oxide mineral core within the central cavity of the protein
CC complex (PubMed:21494619, PubMed:24855650). Retains ferroxidase
CC activity inside the encapsulin nanocompartment with a slight decrease
CC in rate. It is not known if this protein is normally found in the
CC encapsulin nanocompartment (PubMed:24855650).
CC {ECO:0000269|PubMed:21494619, ECO:0000269|PubMed:24855650,
CC ECO:0000305|PubMed:24855650}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O;
CC Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1;
CC Evidence={ECO:0000269|PubMed:21494619, ECO:0000269|PubMed:24855650};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11149;
CC Evidence={ECO:0000269|PubMed:24855650};
CC -!- SUBUNIT: Homooligomer of 24 subunits that are packed together to form
CC an approximately spherical molecule 12-13 nm in diameter with a central
CC cavity, in which large amounts of iron can be stored.
CC {ECO:0000269|PubMed:21494619, ECO:0000269|PubMed:34342280,
CC ECO:0000305|PubMed:21139218}.
CC -!- SUBCELLULAR LOCATION: Encapsulin nanocompartment
CC {ECO:0000269|PubMed:24855650}. Note=Forms an approximately 12 nm shell
CC inside the encapsulin nanocompartment, suggesting the latter
CC encapsulates the entire 24-subunit homooligomer.
CC {ECO:0000305|PubMed:24855650}.
CC -!- INDUCTION: Induced by 1 mM reactive nitrogen intermediate sodium
CC nitroprusside dihydrate (at protein level). Induced by exposure to 50
CC uM FeCl(3). A possible member of the dormancy regulon. Induced in
CC response to reduced oxygen tension (hypoxia), repressed by carbon
CC monoxide (CO). It is hoped that this regulon will give insight into the
CC latent, or dormant phase of infection. {ECO:0000269|PubMed:11416222,
CC ECO:0000269|PubMed:12057942, ECO:0000269|PubMed:12065475,
CC ECO:0000269|PubMed:18474359, ECO:0000269|PubMed:9864257}.
CC -!- DOMAIN: The C-terminus (residues 163-181) targets the protein to the
CC encapsulin nanocompartment (PubMed:24855650). Interestingly the C-
CC terminus is localized iside the ferritin cage, in theory it does not
CC touch the interior of the nanocompartment (PubMed:34342280).
CC {ECO:0000269|PubMed:24855650, ECO:0000269|PubMed:34342280}.
CC -!- DISRUPTION PHENOTYPE: A single deletion is more sensitive to oxidative
CC stress (cumene hydroperoxide but not plumbagin). A double bfrA-bfrB
CC mutant grows 40% less well in the presence of an iron chelator, is more
CC sensitive to oxidative stress, has significantly reduced pathological
CC effects in guinea pigs and a marked reduction in its survival in human
CC macrophages. {ECO:0000269|PubMed:22101841}.
CC -!- BIOTECHNOLOGY: As this protein can be easily produced at high
CC concentrations upon expression in E.coli and is highly stable, it is a
CC good model protein for testing new microscopes.
CC {ECO:0000269|PubMed:34342280}.
CC -!- SIMILARITY: Belongs to the ferritin-like superfamily. Prokaryotic
CC family. {ECO:0000305}.
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DR EMBL; AF102693; AAF06357.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46670.1; -; Genomic_DNA.
DR PIR; F70653; F70653.
DR RefSeq; NP_218358.1; NC_000962.3.
DR RefSeq; WP_003420920.1; NZ_NVQJ01000022.1.
DR PDB; 3QD8; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=1-181.
DR PDB; 3UNO; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=1-181.
DR PDB; 7O6E; EM; 2.10 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/V/W/X/Y=1-181.
DR PDBsum; 3QD8; -.
DR PDBsum; 3UNO; -.
DR PDBsum; 7O6E; -.
DR AlphaFoldDB; P9WNE5; -.
DR SMR; P9WNE5; -.
DR STRING; 83332.Rv3841; -.
DR PaxDb; P9WNE5; -.
DR DNASU; 886176; -.
DR GeneID; 45427842; -.
DR GeneID; 886176; -.
DR KEGG; mtu:Rv3841; -.
DR TubercuList; Rv3841; -.
DR eggNOG; COG1528; Bacteria.
DR OMA; CEDKGFE; -.
DR PhylomeDB; P9WNE5; -.
DR Reactome; R-HSA-1222449; Mtb iron assimilation by chelation.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008199; F:ferric iron binding; IBA:GO_Central.
DR GO; GO:0008198; F:ferrous iron binding; IBA:GO_Central.
DR GO; GO:0004322; F:ferroxidase activity; IDA:MTBBASE.
DR GO; GO:0006880; P:intracellular sequestering of iron ion; IDA:MTBBASE.
DR GO; GO:0006826; P:iron ion transport; IEA:InterPro.
DR GO; GO:0001666; P:response to hypoxia; IDA:MTBBASE.
DR GO; GO:0051409; P:response to nitrosative stress; IEP:MTBBASE.
DR CDD; cd01055; Nonheme_Ferritin; 1.
DR Gene3D; 1.20.1260.10; -; 1.
DR InterPro; IPR001519; Ferritin.
DR InterPro; IPR012347; Ferritin-like.
DR InterPro; IPR009040; Ferritin-like_diiron.
DR InterPro; IPR009078; Ferritin-like_SF.
DR InterPro; IPR008331; Ferritin_DPS_dom.
DR InterPro; IPR041719; Ferritin_prok.
DR PANTHER; PTHR11431; PTHR11431; 1.
DR Pfam; PF00210; Ferritin; 1.
DR SUPFAM; SSF47240; SSF47240; 1.
DR PROSITE; PS50905; FERRITIN_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Encapsulin nanocompartment; Iron;
KW Iron storage; Metal-binding; Oxidoreductase; Reference proteome; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9864257"
FT CHAIN 2..181
FT /note="Bacterioferritin BfrB"
FT /id="PRO_0000392942"
FT DOMAIN 5..150
FT /note="Ferritin-like diiron"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT REGION 163..181
FT /note="Targeting peptide"
FT /evidence="ECO:0000269|PubMed:24855650"
FT BINDING 22
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT BINDING 55
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT BINDING 55
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT BINDING 58
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT BINDING 99
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT BINDING 132
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00085"
FT MUTAGEN 167..181
FT /note="Missing: Protein no longer targeted to encapsulin
FT nanocompartments."
FT /evidence="ECO:0000269|PubMed:24855650"
FT MUTAGEN 168..181
FT /note="Missing: No large change in protein assembly or
FT structure, decreased thermostability, 3.5-fold reduction in
FT oxidation of Fe(2+), 20% reduction in Fe(3+) release rate."
FT /evidence="ECO:0000269|PubMed:21494619"
FT HELIX 10..37
FT /evidence="ECO:0007829|PDB:7O6E"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:7O6E"
FT HELIX 42..68
FT /evidence="ECO:0007829|PDB:7O6E"
FT HELIX 88..116
FT /evidence="ECO:0007829|PDB:7O6E"
FT HELIX 119..149
FT /evidence="ECO:0007829|PDB:7O6E"
FT HELIX 153..163
FT /evidence="ECO:0007829|PDB:7O6E"
SQ SEQUENCE 181 AA; 20442 MW; C0F375669A292F55 CRC64;
MTEYEGPKTK FHALMQEQIH NEFTAAQQYV AIAVYFDSED LPQLAKHFYS QAVEERNHAM
MLVQHLLDRD LRVEIPGVDT VRNQFDRPRE ALALALDQER TVTDQVGRLT AVARDEGDFL
GEQFMQWFLQ EQIEEVALMA TLVRVADRAG ANLFELENFV AREVDVAPAA SGAPHAAGGR
L
