NUCC_PSEAI
ID NUCC_PSEAI Reviewed; 241 AA.
AC P0DTF8;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Endodeoxyribonuclease NucC {ECO:0000303|PubMed:31932165};
DE EC=3.1.-.- {ECO:0000269|PubMed:31932165};
DE AltName: Full=NucC nuclease;
GN Name=nucC {ECO:0000303|PubMed:31932165}; ORFNames=A4W92_29540;
OS Pseudomonas aeruginosa.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=287;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27853 / DSM 1117 / CIP 76.110 / JCM 6119 / LMG 6395 / NCIMB
RC 12469;
RX PubMed=27139485; DOI=10.1128/aac.00434-16;
RA Feng Y., Jonker M.J., Moustakas I., Brul S., Ter Kuile B.H.;
RT "Dynamics of Mutations during Development of Resistance by Pseudomonas
RT aeruginosa against Five Antibiotics.";
RL Antimicrob. Agents Chemother. 60:4229-4236(2016).
RN [2]
RP FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=ATCC 27853 / DSM 1117 / CIP 76.110 / JCM 6119 / LMG 6395 / NCIMB
RC 12469;
RX PubMed=31932165; DOI=10.1016/j.molcel.2019.12.009;
RA Ye Q., Lau R.K., Mathews I.T., Birkholz E.A., Watrous J.D., Azimi C.S.,
RA Pogliano J., Jain M., Corbett K.D.;
RT "HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-
RT like Enzymes to Mediate Bacteriophage Immunity.";
RL Mol. Cell 77:709-722(2020).
RN [3]
RP CLASSIFICATION AND NOMENCLATURE.
RX PubMed=32839535; DOI=10.1038/s41564-020-0777-y;
RA Millman A., Melamed S., Amitai G., Sorek R.;
RT "Diversity and classification of cyclic-oligonucleotide-based anti-phage
RT signalling systems.";
RL Nat. Microbiol. 5:1608-1615(2020).
RN [4] {ECO:0007744|PDB:6Q1H}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 2-241 IN COMPLEX WITH CYCLIC
RP AMP-AMP-AMP, FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=ATCC 27853 / DSM 1117 / CIP 76.110 / JCM 6119 / LMG 6395 / NCIMB
RC 12469;
RX PubMed=31932164; DOI=10.1016/j.molcel.2019.12.010;
RA Lau R.K., Ye Q., Birkholz E.A., Berg K.R., Patel L., Mathews I.T.,
RA Watrous J.D., Ego K., Whiteley A.T., Lowey B., Mekalanos J.J.,
RA Kranzusch P.J., Jain M., Pogliano J., Corbett K.D.;
RT "Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial
RT Endonuclease Mediating Bacteriophage Immunity.";
RL Mol. Cell 77:723-733(2020).
CC -!- FUNCTION: CBASS (cyclic oligonucleotide-based antiphage signaling
CC system) provides immunity against bacteriophage. The CD-NTase protein
CC synthesizes cyclic nucleotides in response to infection; these serve as
CC specific second messenger signals. The signals activate a diverse range
CC of effectors, leading to bacterial cell death and thus abortive phage
CC infection. A type III-C(AAA) CBASS system (PubMed:32839535).
CC {ECO:0000269|PubMed:31932165, ECO:0000303|PubMed:32839535}.
CC -!- FUNCTION: A cyclic nucleotide-activated dsDNase. In the presence of
CC 3',3',3'-cyclic AMP-AMP-AMP (cAAA) and to a lesser extent cyclic-di-AMP
CC (c-di-AMP), endonucleolytically degrades dsDNA (Probable). Binds one
CC cAAA in a pocket on one surface of the trimer; cAAA binding promotes
CC hexamerization which is probably necessary for nuclease activation
CC (PubMed:31932164). The nuclease digests dsDNA to about 50 bp lengths.
CC DNA has been modeled to contact a pair of juxtaposed active sites (one
CC from each layer of the hexamer), accounting for cleavage on both
CC strands (By similarity). {ECO:0000250|UniProtKB:D7Y2H5,
CC ECO:0000269|PubMed:31932164, ECO:0000305|PubMed:31932165}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:D7Y2H5};
CC -!- ACTIVITY REGULATION: Activated by cAAA and to a lesser extent cAA; both
CC cyclic nucleotides are products of its cognate CD-NTase. Cyclic
CC nucleotide binding causes hexamerization.
CC {ECO:0000305|PubMed:31932165}.
CC -!- SUBUNIT: Self-oligomerizes (PubMed:31932165). Forms homotrimers; in the
CC presence of cAAA the trimers associate face-to-face to form
CC homohexamers. The 2 cAAA-binding sites are on the exterior of the
CC hexamer at the three-way junction, there are maximally 2 cyclic
CC nucleotides per hexamer (PubMed:31932164).
CC {ECO:0000269|PubMed:31932164, ECO:0000269|PubMed:31932165}.
CC -!- DOMAIN: Second messenger binding causes a series of shifts that enclose
CC the cAAA molecule. {ECO:0000269|PubMed:31932164}.
CC -!- SIMILARITY: Belongs to the NucC endonuclease family.
CC {ECO:0000305|PubMed:31932164}.
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DR EMBL; CP015117; AMX91007.1; -; Genomic_DNA.
DR RefSeq; WP_003050273.1; NZ_WXZT01000006.1.
DR PDB; 6Q1H; X-ray; 1.45 A; A/B/C/E/F/G=2-241.
DR PDBsum; 6Q1H; -.
DR AlphaFoldDB; P0DTF8; -.
DR SMR; P0DTF8; -.
DR GeneID; 56409846; -.
DR OMA; GGTYPPK; -.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Endonuclease; Hydrolase; Magnesium;
KW Metal-binding; Nuclease; Nucleotide-binding.
FT CHAIN 1..241
FT /note="Endodeoxyribonuclease NucC"
FT /id="PRO_0000451846"
FT ACT_SITE 73
FT /evidence="ECO:0000305|PubMed:31932164"
FT ACT_SITE 104
FT /evidence="ECO:0000305|PubMed:31932164"
FT ACT_SITE 106
FT /evidence="ECO:0000305|PubMed:31932164"
FT BINDING 73
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:D7Y2H5"
FT BINDING 104
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:D7Y2H5"
FT SITE 53
FT /note="Binds cAAA"
FT /evidence="ECO:0000269|PubMed:31932164,
FT ECO:0007744|PDB:6Q1H"
FT SITE 81
FT /note="Binds cAAA"
FT /evidence="ECO:0000269|PubMed:31932164,
FT ECO:0007744|PDB:6Q1H"
FT SITE 136
FT /note="Gate loop latch"
FT /evidence="ECO:0000269|PubMed:31932164,
FT ECO:0007744|PDB:6Q1H"
FT SITE 141
FT /note="Gate loop latch"
FT /evidence="ECO:0000269|PubMed:31932164,
FT ECO:0007744|PDB:6Q1H"
FT SITE 226
FT /note="Binds cAAA"
FT /evidence="ECO:0000269|PubMed:31932164,
FT ECO:0007744|PDB:6Q1H"
FT HELIX 6..27
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 31..49
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 111..125
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 150..162
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 166..173
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:6Q1H"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:6Q1H"
FT TURN 196..199
FT /evidence="ECO:0007829|PDB:6Q1H"
FT STRAND 200..207
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 209..222
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 232..236
FT /evidence="ECO:0007829|PDB:6Q1H"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:6Q1H"
SQ SEQUENCE 241 AA; 26663 MW; 0D42F5846786EEEA CRC64;
MSQWSLSQLL SSLHEDIQQR LSVVRKTFGH PGTKGDASEN VWIDMLDTYL PKRYQAAKAH
VVDSLGNFSQ QIDVVVFDRQ YSPFIFTYEN ETIIPAESVY AVFEAKQTAD AGLVAYAQEK
VASVRRLHRT SLPIPHAGGT YPAKPLIPIL GGLLTFESEW SPALGPSMDK ALNANLTEGR
LDIGCVAAHG HFFYDQASGA YSYTNENKPA TAFLFKLIAQ LQFSGTVPMI DVEAYGQWLT
K
