GAM_LAMBD
ID GAM_LAMBD Reviewed; 138 AA.
AC P03702; Q53285;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Host-nuclease inhibitor protein gam;
GN Name=gam {ECO:0000303|PubMed:6458018}; Synonyms=gamma;
OS Escherichia phage lambda (Bacteriophage lambda).
OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC Caudovirales; Siphoviridae; Lambdavirus.
OX NCBI_TaxID=10710;
OH NCBI_TaxID=562; Escherichia coli.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6458018; DOI=10.1093/nar/9.18.4639;
RA Ineichen K., Shepherd J.C.W., Bickle T.A.;
RT "The DNA sequence of the phage lambda genome between PL and the gene bet.";
RL Nucleic Acids Res. 9:4639-4653(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=6221115; DOI=10.1016/0022-2836(82)90546-0;
RA Sanger F., Coulson A.R., Hong G.F., Hill D.F., Petersen G.B.;
RT "Nucleotide sequence of bacteriophage lambda DNA.";
RL J. Mol. Biol. 162:729-773(1982).
RN [3]
RP PROBABLE ALTERNATIVE TRANSLATION INITATION SITE, FUNCTION, AND ISOFORM
RP GAMS.
RX PubMed=2943636; DOI=10.1016/0378-1119(86)90214-3;
RA Friedman S.A., Hays J.B.;
RT "Selective inhibition of Escherichia coli recBC activities by plasmid-
RT encoded GamS function of phage lambda.";
RL Gene 43:255-263(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1327972; DOI=10.1016/0378-1119(92)90086-5;
RA Maruyama I.N., Brenner S.;
RT "A selective lambda phage cloning vector with automatic excision of the
RT insert in a plasmid.";
RL Gene 120:135-141(1992).
RN [5]
RP PROTEIN SEQUENCE OF 44-55 AND 46-55, PROBABLE ALTERNATIVE TRANSLATION
RP INITATION SITE, FUNCTION, INTERACTION WITH HOST RECBCD, AND ISOFORM GAMS.
RX PubMed=1653221; DOI=10.1128/jb.173.18.5808-5821.1991;
RA Murphy K.C.;
RT "Lambda Gam protein inhibits the helicase and chi-stimulated recombination
RT activities of Escherichia coli RecBCD enzyme.";
RL J. Bacteriol. 173:5808-5821(1991).
RN [6]
RP FUNCTION.
RX PubMed=4275917; DOI=10.1073/pnas.70.8.2215;
RA Sakaki Y., Karu A.E., Linn S., Echols H.;
RT "Purification and properties of the gamma-protein specified by
RT bacteriophage lambda: an inhibitor of the host RecBC recombination
RT enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 70:2215-2219(1973).
RN [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=126236; DOI=10.1016/s0021-9258(19)40955-1;
RA Karu A.E., Sakaki Y., Echols H., Linn S.;
RT "The gamma protein specified by bacteriophage gamma. Structure and
RT inhibitory activity for the recBC enzyme of Escherichia coli.";
RL J. Biol. Chem. 250:7377-7387(1975).
RN [8]
RP FUNCTION.
RX PubMed=33157039; DOI=10.1016/j.cell.2020.09.065;
RA Millman A., Bernheim A., Stokar-Avihail A., Fedorenko T., Voichek M.,
RA Leavitt A., Oppenheimer-Shaanan Y., Sorek R.;
RT "Bacterial Retrons Function In Anti-Phage Defense.";
RL Cell 183:1551-1561(2020).
RN [9] {ECO:0007744|PDB:2UUZ, ECO:0007744|PDB:2UV1}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 40-138 (ISOFORM GAMS), FUNCTION,
RP SUBUNIT, AND INTERACTION WITH HOST RECBCD.
RX PubMed=17544443; DOI=10.1016/j.jmb.2007.05.037;
RA Court R., Cook N., Saikrishnan K., Wigley D.;
RT "The crystal structure of lambda-Gam protein suggests a model for RecBCD
RT inhibition.";
RL J. Mol. Biol. 371:25-33(2007).
RN [10] {ECO:0007744|PDB:5MBV}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 41-138 IN COMPLEX WITH
RP HOST RECBCD, FUNCTION, SUBUNIT, AND INTERACTION WITH HOST RECBCD.
RX PubMed=28009252; DOI=10.7554/elife.22963;
RA Wilkinson M., Troman L., Wan Nur Ismah W.A., Chaban Y., Avison M.B.,
RA Dillingham M.S., Wigley D.B.;
RT "Structural basis for the inhibition of RecBCD by Gam and its synergistic
RT antibacterial effect with quinolones.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Both GamL and GamS bind to host RecBCD nuclease and inhibit
CC its activities, protecting the viral DNA against RecBCD mediated
CC degradation (PubMed:2943636, PubMed:4275917, PubMed:126236,
CC PubMed:1653221, PubMed:17544443). Isoform GamS mimics DNA, preventing
CC RecBCD from binding DNA (PubMed:17544443, PubMed:28009252). Expression
CC of this protein in E.coli renders cells more sensitive to
CC fluoroquinolone antibiotics (which inhibit topoisomerases and induce
CC dsDNA breaks) (PubMed:28009252). Frameshift mutations that delete most
CC of this protein (starting from position 78 or 97 of GamL) allow the
CC bacteriophage to overcome the retron Ec48 bacteriophage defense system.
CC Overexpression of the wild-type gam protein in E.coli with an intact
CC Ec48 retron leads to a dramatic decrease in cell growth, the frameshift
CC mutants do not have this effect (PubMed:33157039).
CC {ECO:0000269|PubMed:126236, ECO:0000269|PubMed:1653221,
CC ECO:0000269|PubMed:17544443, ECO:0000269|PubMed:28009252,
CC ECO:0000269|PubMed:2943636, ECO:0000269|PubMed:33157039,
CC ECO:0000269|PubMed:4275917}.
CC -!- SUBUNIT: Homodimer (PubMed:126236, PubMed:17544443, PubMed:28009252).
CC Interacts with host RecBCD without displacing any of the subunits; this
CC interaction prevents RecBCD from binding to DNA (PubMed:1653221,
CC PubMed:17544443, PubMed:28009252). The GamS isoform makes extensive
CC contacts with RecB, and inserts deeply into the RecBCD complex
CC (PubMed:28009252). {ECO:0000269|PubMed:126236,
CC ECO:0000269|PubMed:1653221, ECO:0000269|PubMed:17544443,
CC ECO:0000269|PubMed:28009252}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=GamL {ECO:0000305|PubMed:1653221};
CC IsoId=P03702-1; Sequence=Displayed;
CC Name=GamS {ECO:0000269|PubMed:1653221, ECO:0000269|PubMed:2943636};
CC IsoId=P03702-2; Sequence=VSP_061538;
CC -!- PTM: 2 forms, GamL and GamS are isolated from overproducing cells; the
CC shorter form (GamS) is more abundant. As both have good ribosome-
CC binding sites they may be independently translated. GamS is processed
CC at the N-terminus and starts on Tyr-44 and Ile-46; both start sites are
CC present in equal amounts (PubMed:1653221). In cells with an induced
CC lambda prophage a protein consistent with the size of GamL was isolated
CC (PubMed:126236). {ECO:0000269|PubMed:126236,
CC ECO:0000269|PubMed:1653221}.
CC -!- CAUTION: Originally (PubMed:6458018) the gam gene product was assigned
CC to the sequence shown and it was suggested that the gene kil protein is
CC encoded from within this gene and corresponds to residues 41-138 (now
CC called GamS). For an alternative assignment of this gene see the entry
CC for the kil gene protein of lambda. {ECO:0000305|PubMed:6458018}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA23977.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; V00638; CAA23978.1; -; Genomic_DNA.
DR EMBL; V00638; CAA23977.1; ALT_INIT; Genomic_DNA.
DR EMBL; J02459; AAA96571.1; -; Genomic_DNA.
DR EMBL; S46756; AAB23852.2; -; Genomic_DNA.
DR PIR; D93737; QGBPL.
DR RefSeq; NP_040618.1; NC_001416.1.
DR PDB; 2UUZ; X-ray; 2.30 A; A/B=40-138.
DR PDB; 2UV1; X-ray; 2.60 A; A/B=40-138.
DR PDB; 5MBV; EM; 3.80 A; A/E=41-138.
DR PDBsum; 2UUZ; -.
DR PDBsum; 2UV1; -.
DR PDBsum; 5MBV; -.
DR SMR; P03702; -.
DR DIP; DIP-572N; -.
DR GeneID; 2703509; -.
DR KEGG; vg:2703509; -.
DR EvolutionaryTrace; P03702; -.
DR Proteomes; UP000001711; Genome.
DR GO; GO:0060703; F:deoxyribonuclease inhibitor activity; IDA:CACAO.
DR GO; GO:0099016; P:evasion by virus of DNA end degradation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.2020; -; 1.
DR InterPro; IPR009274; Gam.
DR InterPro; IPR042034; Gam_sf.
DR Pfam; PF06064; Gam; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Direct protein sequencing;
KW DNA end degradation evasion by virus; Host-virus interaction;
KW Reference proteome.
FT CHAIN 1..138
FT /note="Host-nuclease inhibitor protein gam"
FT /id="PRO_0000077641"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform GamS)"
FT /evidence="ECO:0000269|PubMed:1653221"
FT /id="VSP_061538"
FT CONFLICT 79
FT /note="L -> I (in Ref. 4; AAB23852)"
FT /evidence="ECO:0000305"
FT HELIX 50..76
FT /evidence="ECO:0007829|PDB:2UUZ"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:2UUZ"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:2UUZ"
FT HELIX 99..107
FT /evidence="ECO:0007829|PDB:2UUZ"
FT HELIX 110..135
FT /evidence="ECO:0007829|PDB:2UUZ"
SQ SEQUENCE 138 AA; 16346 MW; 19479118D37F576C CRC64;
MDINTETEIK QKHSLTPFPV FLISPAFRGR YFHSYFRSSA MNAYYIQDRL EAQSWARHYQ
QLAREEKEAE LADDMEKGLP QHLFESLCID HLQRHGASKK SITRAFDDDV EFQERMAEHI
RYMVETIAHH QVDIDSEV
