PPE41_MYCTU
ID PPE41_MYCTU Reviewed; 194 AA.
AC Q79FE1; F2GHN8; I6YDD9;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=PPE family protein PPE41 {ECO:0000305};
GN Name=PPE41 {ECO:0000312|EMBL:CCP45222.1};
GN OrderedLocusNames=Rv2430c {ECO:0000312|EMBL:CCP45222.1};
GN ORFNames=LH57_13290 {ECO:0000312|EMBL:AIR15197.1};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=17076665; DOI=10.1111/j.1365-2958.2006.05409.x;
RA Abdallah A.M., Verboom T., Hannes F., Safi M., Strong M., Eisenberg D.,
RA Musters R.J., Vandenbroucke-Grauls C.M., Appelmelk B.J., Luirink J.,
RA Bitter W.;
RT "A specific secretion system mediates PPE41 transport in pathogenic
RT mycobacteria.";
RL Mol. Microbiol. 62:667-679(2006).
RN [4]
RP FUNCTION.
RX PubMed=18974870; DOI=10.1371/journal.pone.0003586;
RA Tundup S., Pathak N., Ramanadham M., Mukhopadhyay S., Murthy K.J.,
RA Ehtesham N.Z., Hasnain S.E.;
RT "The co-operonic PE25/PPE41 protein complex of Mycobacterium tuberculosis
RT elicits increased humoral and cell mediated immune response.";
RL PLoS ONE 3:E3586-E3586(2008).
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 SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=22340629; DOI=10.1111/j.1365-2958.2012.08001.x;
RA Bottai D., Di Luca M., Majlessi L., Frigui W., Simeone R., Sayes F.,
RA Bitter W., Brennan M.J., Leclerc C., Batoni G., Campa M., Brosch R.,
RA Esin S.;
RT "Disruption of the ESX-5 system of Mycobacterium tuberculosis causes loss
RT of PPE protein secretion, reduction of cell wall integrity and strong
RT attenuation.";
RL Mol. Microbiol. 83:1195-1209(2012).
RN [7]
RP FUNCTION.
RX PubMed=25379378; DOI=10.1016/j.fob.2014.09.001;
RA Tundup S., Mohareer K., Hasnain S.E.;
RT "Mycobacterium tuberculosis PE25/PPE41 protein complex induces necrosis in
RT macrophages: Role in virulence and disease reactivation?";
RL FEBS Open Bio 4:822-828(2014).
RN [8]
RP FUNCTION.
RC STRAIN=H37Rv;
RX PubMed=26318856; DOI=10.1007/s00430-015-0434-x;
RA Chen W., Bao Y., Chen X., Burton J., Gong X., Gu D., Mi Y., Bao L.;
RT "Mycobacterium tuberculosis PE25/PPE41 protein complex induces activation
RT and maturation of dendritic cells and drives Th2-biased immune responses.";
RL Med. Microbiol. Immunol. 205:119-131(2016).
RN [9] {ECO:0007744|PDB:2G38}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH PE25, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=16690741; DOI=10.1073/pnas.0602606103;
RA Strong M., Sawaya M.R., Wang S., Phillips M., Cascio D., Eisenberg D.;
RT "Toward the structural genomics of complexes: crystal structure of a PE/PPE
RT protein complex from Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:8060-8065(2006).
RN [10] {ECO:0007744|PDB:4KXR}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH PE25 AND ESPG5,
RP SUBUNIT, AND MUTAGENESIS OF ALA-124; LEU-125; GLN-127; 129-THR-ALA-130 AND
RP ALA-130.
RX PubMed=25155747; DOI=10.1111/mmi.12770;
RA Korotkova N., Freire D., Phan T.H., Ummels R., Creekmore C.C., Evans T.J.,
RA Wilmanns M., Bitter W., Parret A.H., Houben E.N., Korotkov K.V.;
RT "Structure of the Mycobacterium tuberculosis type VII secretion system
RT chaperone EspG5 in complex with PE25-PPE41 dimer.";
RL Mol. Microbiol. 94:367-382(2014).
RN [11] {ECO:0007744|PDB:4W4K, ECO:0007744|PDB:4W4L}
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) IN COMPLEX WITH PE25 AND IN COMPLEX
RP WITH PE25 AND ESPG5, AND SUBUNIT.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=25275011; DOI=10.1073/pnas.1409345111;
RA Ekiert D.C., Cox J.S.;
RT "Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals
RT molecular specificity of ESX protein secretion.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:14758-14763(2014).
CC -!- FUNCTION: The PE25/PPE41 dimer induces both a strong humoral and
CC cellular immune response (PubMed:18974870). The dimer induces necrosis,
CC but not apoptosis, in mouse macrophage cells (PubMed:25379378). It also
CC induces activation and maturation of mouse dendritic cells and drives
CC Th2-biased immune responses (PubMed:26318856).
CC {ECO:0000269|PubMed:18974870, ECO:0000269|PubMed:25379378,
CC ECO:0000269|PubMed:26318856}.
CC -!- SUBUNIT: Forms a heterodimer with PE25. The dimer forms a 1:1:1
CC heterotrimeric complex with EspG5. PPE41 interacts directly with EspG5.
CC {ECO:0000269|PubMed:16690741, ECO:0000269|PubMed:25155747,
CC ECO:0000269|PubMed:25275011}.
CC -!- INTERACTION:
CC Q79FE1; I6X486: PE25; NbExp=3; IntAct=EBI-8063017, EBI-15582196;
CC Q79FE1; Q7D756: MT2506; Xeno; NbExp=4; IntAct=EBI-8063017, EBI-8063031;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17076665,
CC ECO:0000269|PubMed:22340629}. Cell surface
CC {ECO:0000269|PubMed:17076665, ECO:0000269|PubMed:22340629}.
CC Note=Secreted via the ESX-5 / type VII secretion system (T7SS).
CC {ECO:0000269|PubMed:17076665, ECO:0000269|PubMed:22340629}.
CC -!- SIMILARITY: Belongs to the mycobacterial PPE family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45222.1; -; Genomic_DNA.
DR EMBL; CP009480; AIR15197.1; -; Genomic_DNA.
DR RefSeq; WP_003412549.1; NZ_NVQJ01000024.1.
DR RefSeq; YP_177881.1; NC_000962.3.
DR PDB; 2G38; X-ray; 2.20 A; B/D=1-194.
DR PDB; 4KXR; X-ray; 2.60 A; B=1-194.
DR PDB; 4W4K; X-ray; 1.95 A; B/D=1-174.
DR PDB; 4W4L; X-ray; 2.45 A; B=1-174.
DR PDB; 6VJ5; X-ray; 2.40 A; B=1-194.
DR PDBsum; 2G38; -.
DR PDBsum; 4KXR; -.
DR PDBsum; 4W4K; -.
DR PDBsum; 4W4L; -.
DR PDBsum; 6VJ5; -.
DR AlphaFoldDB; Q79FE1; -.
DR SASBDB; Q79FE1; -.
DR SMR; Q79FE1; -.
DR DIP; DIP-42564N; -.
DR IntAct; Q79FE1; 2.
DR MINT; Q79FE1; -.
DR STRING; 83332.Rv2430c; -.
DR PaxDb; Q79FE1; -.
DR DNASU; 885945; -.
DR GeneID; 45426420; -.
DR GeneID; 885945; -.
DR KEGG; mtu:Rv2430c; -.
DR PATRIC; fig|83332.111.peg.2717; -.
DR TubercuList; Rv2430c; -.
DR eggNOG; COG5651; Bacteria.
DR HOGENOM; CLU_000243_10_2_11; -.
DR PhylomeDB; Q79FE1; -.
DR EvolutionaryTrace; Q79FE1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IBA:GO_Central.
DR Gene3D; 1.20.1260.20; -; 1.
DR InterPro; IPR000030; PPE_family.
DR InterPro; IPR038332; PPE_sf.
DR Pfam; PF00823; PPE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Secreted; Virulence.
FT CHAIN 1..194
FT /note="PPE family protein PPE41"
FT /id="PRO_0000435111"
FT MUTAGEN 124
FT /note="A->L: Does not disrupt the interaction with EspG5."
FT /evidence="ECO:0000269|PubMed:25155747"
FT MUTAGEN 125
FT /note="L->E,R: Does not affect formation of the PE25/PPE41
FT dimer, but abolishes EspG5 binding to PE25/PPE41."
FT /evidence="ECO:0000269|PubMed:25155747"
FT MUTAGEN 127
FT /note="Q->I: Does not disrupt the interaction with EspG5."
FT /evidence="ECO:0000269|PubMed:25155747"
FT MUTAGEN 129..130
FT /note="TA->DR: Does not affect formation of the PE25/PPE41
FT dimer, but abolishes EspG5 binding to PE25/PPE41."
FT /evidence="ECO:0000269|PubMed:25155747"
FT MUTAGEN 130
FT /note="A->I: Does not disrupt the interaction with EspG5."
FT /evidence="ECO:0000269|PubMed:25155747"
FT HELIX 3..5
FT /evidence="ECO:0007829|PDB:6VJ5"
FT HELIX 8..17
FT /evidence="ECO:0007829|PDB:2G38"
FT HELIX 22..49
FT /evidence="ECO:0007829|PDB:2G38"
FT TURN 50..55
FT /evidence="ECO:0007829|PDB:2G38"
FT HELIX 59..67
FT /evidence="ECO:0007829|PDB:2G38"
FT HELIX 69..102
FT /evidence="ECO:0007829|PDB:2G38"
FT HELIX 106..121
FT /evidence="ECO:0007829|PDB:2G38"
FT HELIX 129..162
FT /evidence="ECO:0007829|PDB:2G38"
SQ SEQUENCE 194 AA; 21943 MW; 85F63AA653B04D75 CRC64;
MHFEAYPPEV NSANIYAGPG PDSMLAAARA WRSLDVEMTA VQRSFNRTLL SLMDAWAGPV
VMQLMEAAKP FVRWLTDLCV QLSEVERQIH EIVRAYEWAH HDMVPLAQIY NNRAERQILI
DNNALGQFTA QIADLDQEYD DFWDEDGEVM RDYRLRVSDA LSKLTPWKAP PPIAHSTVLV
APVSPSTASS RTDT
