LSR2_MYCTU
ID LSR2_MYCTU Reviewed; 112 AA.
AC P9WIP7; L0TG69; O06285; P65648;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Nucleoid-associated protein Lsr2;
GN Name=lsr2; OrderedLocusNames=Rv3597c; ORFNames=MTCY07H7B.25;
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 FUNCTION, AND DNA-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17590082; DOI=10.1371/journal.ppat.0030087;
RA Colangeli R., Helb D., Vilcheze C., Hazbon M.H., Lee C.G., Safi H.,
RA Sayers B., Sardone I., Jones M.B., Fleischmann R.D., Peterson S.N.,
RA Jacobs W.R. Jr., Alland D.;
RT "Transcriptional regulation of multi-drug tolerance and antibiotic-induced
RT responses by the histone-like protein Lsr2 in M. tuberculosis.";
RL PLoS Pathog. 3:E87-E87(2007).
RN [3]
RP FUNCTION, DNA-BINDING, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF ASP-28; ARG-45; ARG-84 AND PRO-101.
RX PubMed=18187505; DOI=10.1093/nar/gkm1162;
RA Chen J.M., Ren H., Shaw J.E., Wang Y.J., Li M., Leung A.S., Tran V.,
RA Berbenetz N.M., Kocincova D., Yip C.M., Reyrat J.M., Liu J.;
RT "Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein.";
RL Nucleic Acids Res. 36:2123-2135(2008).
RN [4]
RP FUNCTION IN PROTECTION AGAINST REACTIVE OXYGEN INTERMEDIATES.
RX PubMed=19237572; DOI=10.1073/pnas.0810126106;
RA Colangeli R., Haq A., Arcus V.L., Summers E., Magliozzo R.S., McBride A.,
RA Mitra A.K., Radjainia M., Khajo A., Jacobs W.R. Jr., Salgame P., Alland D.;
RT "The multifunctional histone-like protein Lsr2 protects mycobacteria
RT against reactive oxygen intermediates.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4414-4418(2009).
RN [5]
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 [6]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF 97-ARG--ARG-99; ARG-97 AND
RP ARG-99.
RX PubMed=21673140; DOI=10.1073/pnas.1102544108;
RA Gordon B.R., Li Y., Cote A., Weirauch M.T., Ding P., Hughes T.R.,
RA Navarre W.W., Xia B., Liu J.;
RT "Structural basis for recognition of AT-rich DNA by unrelated xenogeneic
RT silencing proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10690-10695(2011).
RN [7]
RP FUNCTION, REGULON, DISRUPTION PHENOTYPE, AND VIRULENCE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=24895305; DOI=10.1128/mbio.01106-14;
RA Bartek I.L., Woolhiser L.K., Baughn A.D., Basaraba R.J., Jacobs W.R. Jr.,
RA Lenaerts A.J., Voskuil M.I.;
RT "Mycobacterium tuberculosis Lsr2 is a global transcriptional regulator
RT required for adaptation to changing oxygen levels and virulence.";
RL MBio 5:E01106-E01114(2014).
RN [8]
RP STRUCTURE BY NMR OF 66-112, FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20133735; DOI=10.1073/pnas.0913551107;
RA Gordon B.R., Li Y., Wang L., Sintsova A., van Bakel H., Tian S.,
RA Navarre W.W., Xia B., Liu J.;
RT "Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and
RT virulence genes in Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:5154-5159(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 1-61, SUBUNIT, DOMAIN, AND
RP POST-TRANSLATIONAL MODIFICATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22719899; DOI=10.1371/journal.pone.0038542;
RA Summers E.L., Meindl K., Uson I., Mitra A.K., Radjainia M., Colangeli R.,
RA Alland D., Arcus V.L.;
RT "The structure of the oligomerization domain of Lsr2 from Mycobacterium
RT tuberculosis reveals a mechanism for chromosome organization and
RT protection.";
RL PLoS ONE 7:E38542-E38542(2012).
CC -!- FUNCTION: DNA-bridging protein that has both architectural and
CC regulatory roles (PubMed:18187505). Influences the organization of
CC chromatin and gene expression by binding non-specifically to DNA, with
CC a preference for AT-rich sequences, and bridging distant DNA segments
CC (PubMed:20133735). Binds in the minor groove of AT-rich DNA
CC (PubMed:21673140). Represses expression of multiple genes involved in a
CC broad range of cellular processes, including major virulence factors or
CC antibiotic-induced genes, such as iniBAC or efpA (PubMed:17590082), and
CC genes important for adaptation of changing O(2) levels
CC (PubMed:24895305). May also activate expression of some gene
CC (PubMed:24895305). May coordinate global gene regulation and virulence
CC (PubMed:20133735). Also protects mycobacteria against reactive oxygen
CC intermediates during macrophage infection by acting as a physical
CC barrier to DNA degradation (PubMed:19237572); the physical protection
CC has been questioned (PubMed:24895305). A strain overexpressing this
CC protein consumes O(2) more slowly than wild-type (PubMed:24895305).
CC {ECO:0000269|PubMed:17590082, ECO:0000269|PubMed:18187505,
CC ECO:0000269|PubMed:19237572, ECO:0000269|PubMed:20133735,
CC ECO:0000269|PubMed:21673140, ECO:0000269|PubMed:24895305}.
CC -!- SUBUNIT: Homodimer. May form higher oligomers via protease-activation.
CC {ECO:0000269|PubMed:18187505, ECO:0000269|PubMed:22719899}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, nucleoid {ECO:0000269|PubMed:18187505,
CC ECO:0000269|PubMed:20133735}.
CC -!- DOMAIN: The C-terminal domain binds DNA and the N-terminal domain is
CC involved in dimerization. Both domains are essential for normal
CC function. {ECO:0000269|PubMed:18187505, ECO:0000269|PubMed:20133735,
CC ECO:0000269|PubMed:22719899}.
CC -!- PTM: The three N-terminal residues may be cleaved by proteases in
CC response to external stress. This cleavage may be required for
CC oligomerization, which leads to chromosome compaction and protection.
CC {ECO:0000269|PubMed:22719899}.
CC -!- DISRUPTION PHENOTYPE: No visible effect on nucleoid structure during
CC anaerobic growth by whole cell staining. Sensitive to atmospheric O(2)
CC levels, at 2% O(2) no difference in growth up to 14 days; required for
CC adaptation to anaerobiosis, at 21 days nearly 1000-fold decrease in
CC survival under anaerobic conditions. Consumes O(2) more rapidly. Has a
CC significant lag in recovery from 7 or 14 days anaerobic growth.
CC Decreased virulence in lungs of BALB/c mice; no visible lung disease at
CC any time point. Increased sensitivity to reactive nitrogen species, not
CC more sensitive to H(2)O(2) or mitomycin (PubMed:24895305).
CC {ECO:0000269|PubMed:24895305}.
CC -!- SIMILARITY: Belongs to the Lsr2 family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46420.1; -; Genomic_DNA.
DR PIR; F70954; F70954.
DR RefSeq; NP_218114.1; NC_000962.3.
DR RefSeq; WP_003419513.1; NZ_NVQJ01000056.1.
DR PDB; 2KNG; NMR; -; A=66-112.
DR PDB; 4E1P; X-ray; 1.73 A; A/B=1-61.
DR PDB; 4E1R; X-ray; 2.04 A; A/B=1-61.
DR PDB; 6QKP; NMR; -; A=74-112.
DR PDB; 6QKQ; NMR; -; A=74-111.
DR PDBsum; 2KNG; -.
DR PDBsum; 4E1P; -.
DR PDBsum; 4E1R; -.
DR PDBsum; 6QKP; -.
DR PDBsum; 6QKQ; -.
DR AlphaFoldDB; P9WIP7; -.
DR BMRB; P9WIP7; -.
DR SMR; P9WIP7; -.
DR STRING; 83332.Rv3597c; -.
DR DrugBank; DB05154; Pretomanid.
DR PaxDb; P9WIP7; -.
DR DNASU; 885580; -.
DR GeneID; 45427584; -.
DR GeneID; 885580; -.
DR KEGG; mtu:Rv3597c; -.
DR TubercuList; Rv3597c; -.
DR eggNOG; ENOG5032RKK; Bacteria.
DR OMA; PIREWAR; -.
DR PhylomeDB; P9WIP7; -.
DR PHI-base; PHI:3077; -.
DR PHI-base; PHI:3632; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009295; C:nucleoid; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR GO; GO:0071453; P:cellular response to oxygen levels; IMP:UniProtKB.
DR GO; GO:0042262; P:DNA protection; IDA:MTBBASE.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MTBBASE.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:MTBBASE.
DR GO; GO:0010039; P:response to iron ion; IEP:MTBBASE.
DR Gene3D; 3.30.60.230; -; 1.
DR Gene3D; 4.10.320.10; -; 1.
DR InterPro; IPR036625; E3-bd_dom_sf.
DR InterPro; IPR024412; Lsr2.
DR InterPro; IPR042261; Lsr2_dimerization.
DR Pfam; PF11774; Lsr2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA-binding; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Virulence.
FT CHAIN 1..112
FT /note="Nucleoid-associated protein Lsr2"
FT /id="PRO_0000021625"
FT DNA_BIND 97..102
FT /evidence="ECO:0000305|PubMed:21673140"
FT REGION 57..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 28
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18187505"
FT MUTAGEN 45
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18187505"
FT MUTAGEN 84
FT /note="R->A: Loss of activity. Can form dimers but does not
FT bind DNA."
FT /evidence="ECO:0000269|PubMed:18187505"
FT MUTAGEN 97..99
FT /note="RGR->AGA: Loss of DNA-binding, in fragment 66-112."
FT /evidence="ECO:0000269|PubMed:21673140"
FT MUTAGEN 97
FT /note="R->A: Reduced DNA-binding, in fragment 66-112."
FT /evidence="ECO:0000269|PubMed:21673140"
FT MUTAGEN 99
FT /note="R->A: Reduced DNA-binding, in fragment 66-112."
FT /evidence="ECO:0000269|PubMed:21673140"
FT MUTAGEN 101
FT /note="P->A: No change in activity. Can still bind DNA and
FT form dimers."
FT /evidence="ECO:0000269|PubMed:18187505"
FT TURN 12..14
FT /evidence="ECO:0007829|PDB:4E1P"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:4E1P"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:4E1P"
FT STRAND 30..36
FT /evidence="ECO:0007829|PDB:4E1P"
FT HELIX 38..54
FT /evidence="ECO:0007829|PDB:4E1P"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:4E1P"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:2KNG"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:6QKP"
FT HELIX 79..89
FT /evidence="ECO:0007829|PDB:2KNG"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:2KNG"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:2KNG"
SQ SEQUENCE 112 AA; 12098 MW; A4B32E478CBAC3E4 CRC64;
MAKKVTVTLV DDFDGSGAAD ETVEFGLDGV TYEIDLSTKN ATKLRGDLKQ WVAAGRRVGG
RRRGRSGSGR GRGAIDREQS AAIREWARRN GHNVSTRGRI PADVIDAYHA AT
