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Supplementary Material Bacterial Death and TRADD-N Domains Help Define Novel Apoptosis and Immunity Mechanisms Shared by Prokary

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Supplementary Material Bacterial Death and TRADD-N Domains Help Define Novel Apoptosis and Immunity Mechanisms Shared by Prokary Supplementary Material Bacterial Death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans Gurmeet Kaur†, Lakshminarayan M. Iyer†, A. Maxwell Burroughs, L. Aravind* Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA †These authors contributed equally to the manuscript Abstract Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retro- viruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring under-appreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic-acid- receptors) and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter. Supplementary Material Bacterial Death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans Figure 6-Source data 1 Gurmeet Kaur†, Lakshminarayan M. Iyer†, A. Maxwell Burroughs, L. Aravind* Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA †These authors contributed equally to the manuscript Index. 1. Source data. Gene neighborhoods and domain architectures of the bacterial GT4-like glycosyltransferases described in this study 2. Source data. Domain architectures of eukaryotic GT4s with a special emphasis on the LSE in Acropora. 3. Source data. Gene neighborhoods and domain architectures of the MNS-like STAND domains (nSTAND2) that is present in a 2-gene operon system each containing a STAND NTPase 4. Source data. Gene neighborhoods and domain architectures of prokaryotic AP-GTPases described in this study Source data. Gene neighborhoods and domain architectures of the bacterial GT4-like glycosyltransferases described in this study acc operon architecture len gen.name taxend species defline gca ADU34882.1 GT4+B12-binding+RADICAL-SAM*→ GT4+B12-binding+RADICAL-SAM 1405 Varpa_0662 Betapro- Variovorax Radical SAM GCA_000184745.1 teobacteria paradoxus EPS domain protein [Variovorax paradoxus EPS] AEV82483.1 WXG+GT4+GT4+REase*→ WXG+GT4+GT4+REase 4143 inaW Actinobacte- Actinoplanes sp. Ice nucleation GCA_000237145.1 ria SE50/110 protein [Actinoplanes sp. SE50/110] AMB84622.1 APATPase+GT4*→ APATPase+GT4 1299 AWM79_04595 Gammapro- Pseudomonas hypothetical GCA_001543125.1 teobacteria agarici protein AWM79_04595 [Pseudomonas agarici] ANP51773.1 Caspase+NACHT+GT4*→||||<-?<-?<-?||?→?→||||<-?<-MFS Caspase+NACHT+GT4 1134 AVL59_21225 Actinobacte- Streptomyces hypothetical GCA_001542625.2 ria griseochromogenes protein AVL59_21225 [Streptomyces griseochromo- genes] AWZ06155.1 Caspase+NACHT+GT4*→||||<-?<-?<-?<-?||APATPase→ Caspase+NACHT+GT4 1156 DRB89_17720 Actinobacte- Streptomyces sp. hypothetical GCA_003287915.1 ria ICC4 protein DRB89_17720 [Streptomyces sp. ICC4] BAO61700.1 SWACOS+GT4*→?→?→||||<-?<-?||MFS→ SWACOS+GT4 1084 PPC_2353 Gammapro- Pseudomonas hypothetical GCA_000828695.1 teobacteria protegens Cab57 protein PPC_2353 [Pseudomonas protegens Cab57] CEL20906.1 ART+Caspase+GT4*→?→ GT4→ ART+Caspase+GT4 1145 BN1199_RS39095Actinobacte- Kibdelospo- hypothetical GCA_000826545.1 ria rangium sp. protein [Kibde- MJ126-NF4 losporangium sp. MJ126-NF4] CUU59694.1 TPR+Caspase→ TPR+Caspase→||||<-CATASP||CATRA-N+CATRA-C+GT4*→||||<-?||HTH+APATPase+TPR→ CATRA-N+CATRA-C+GT4 904 Ga0074812_13074Actinobacte- Frankia irregularis Glycosyltrans- GCA_001536285.1 ria ferase involved in cell wall bisynthesis [Frankia irregularis] EIV94947.1 CATRA-N+CATRA-C+GT4*→||||<-TPR+Caspase<-?<-?<-?<-?||APATPase+TPR→ CATASP→ CATRA-N+CATRA-C+GT4 810 FraQA3DRAFT_4743Actinobacte- Frankia sp. QA3 glycosyltrans- GCA_000262465.1 ria ferase [Frankia sp. QA3] 1 acc operon architecture len gen.name taxend species defline gca EKX63918.1 ZetaToxin+GT4+NUDIX+ART+NTase*→?→?→||||<-Caspase<-?||?→?→||||<-NLPC ZetaToxin+GT4+NUDIX+ART+NTase 2156 STRIP9103_04937Actinobacte- Streptomyces hydrolase, NUDIX GCA_000317595.1 ria ipomoeae 91-03 family [Streptomyces ipomoeae 91-03] EWM12074.1 <-CATASP||CATRA-N+CATRA-C+GT4*→||||<-HTH+APATPase+TPR CATRA-N+CATRA-C+GT4 750 KUTG_02378 Actinobacte- Kutzneria sp. 744 LigA protein GCA_000568255.1 ria [Kutzneria sp. 744] GBE24927.1 Asparaginase_II→ Acetyltransf_6→ GT4*→?→?→?→||||<-?<-SIG+TM+TM+TM<-THUMP+ThiI GT4 407 mshA unclassified bacterium D-inositol GCA_002898115.1 Bacteria BMS3Bbin02 3-phosphate gly- cosyltransferase [bacterium BMS3Bbin02] HBN24878.1 GT4*→ GT4 721 DD447_07855 Firmicutes Lachnospiraceae TPA: hypothetical GCA_003503295.1 bacterium protein DD447_07855 [Lachnospiraceae bacterium] HCI14011.1 GT4+APATPase+TPR*→ GT4+APATPase+TPR 1340 DFK12_08625 Betapro- Gallionellaceae TPA: hypothetical GCA_003521785.1 teobacteria bacterium protein DFK12_08625 [Gallionellaceae bacterium] HCS09332.1 <-MODE-HTH+PBPII||?→||||<-?<-PSE<-PrpF||?→ PSE→ STAND+TPR+GT4*→ STAND+TPR+GT4 1081 DIW67_19725 Gammapro- Pseudomonas sp. TPA: glycosyl- GCA_003531165.1 teobacteria transferase [Pseudomonas sp.] HDL41796.1 GT4*→ GT4 345 ENG98_02120 Actinobacte- Actinobacteria TPA: glycosyl- GCA_011041235.1 ria bacterium transferase, partial [Actinobacteria bacterium] KDN80799.1 MNS+GT4*→||||<-?||?→ ABC_tran→ MNS+GT4 1137 KCH_74340 Actinobacte- Kitasatospora hypothetical GCA_000696185.1 ria cheerisanensis protein KCTC 2395 KCH_74340 [Kitasatospora cheerisanensis KCTC 2395] KNY05162.1 GT4*→ GT4 533 AKH00_12305 Actinobacte- Microbacterium hypothetical GCA_001262495.1 ria sp. GCS4 protein AKH00_12305 [Microbacterium sp. GCS4] KOX13006.1 <-ABC_tran||?→?→||||<-?<-TIR+NACHT||HTH+APATPase+TPR+GT4*→ HTH+APATPase+TPR+GT4 1158 ADK67_45665 Actinobacte- Saccharothrix sp. NTPase GCA_001280085.1 ria NRRL B-16348 [Saccharothrix sp. NRRL B-16348] KQM59620.1 GT4*→||||<-TRPR-HTH+PBPI<-?<-?<-?<-?||PSE→?→ PfkB→ GT4 155 ASE64_09860 Actinobacte- Agreia sp. hypothetical GCA_001421485.1 ria Leaf210 protein ASE64_09860 [Agreia sp. Leaf210] 2 acc operon architecture len gen.name taxend species defline gca KQW27056.1 STAND+GT4*→ STAND+GT4 1005 ASC85_27055 Gammapro- Pseudomonas sp. hypothetical GCA_001425105.1 teobacteria Root401 protein ASC85_27055 [Pseudomonas sp. Root401] KVF32402.1 <-SIG+RCDG1+YidC_periplas+60KD_IMP<-?<-?<-?||?→?→?→ GT4+B12-binding+RADICAL-SAM*→||||<-rve_3 GT4+B12-binding+RADICAL-SAM 1400 WJ08_12515 Betapro- Burkholderia radical SAM GCA_001524025.1 teobacteria vietnamiensis protein [Burkholderia vietnamiensis] KVM90153.1 GT4+B12-binding+RADICAL-SAM*→ GT4+B12-binding+RADICAL-SAM 1404 WT05_03580 Betapro- Burkholderia radical SAM GCA_001527545.1 teobacteria stagnalis protein [Burkholderia stagnalis] KVM94412.1 TniB→?→ NLPC→||||<-?||?→ GT4+B12-binding+RADICAL-SAM*→ GT4+B12-binding+RADICAL-SAM 1404 WT07_28140 Betapro- Burkholderia radical SAM GCA_001527585.1 teobacteria stagnalis protein [Burkholderia stagnalis] KVX13946.1 GT4*→||||<-?||ABhydrolase→||||<-TRANSGLUTAMINASE GT4 282 WL03_19390 Betapro- Burkholderia hypothetical GCA_001539165.1 teobacteria ubonensis protein WL03_19390 [Burkholderia ubonensis] KVZ11040.1 GT4+APATPase+TPR+TPR*→ GT4+APATPase+TPR+TPR 1278 WL11_04565 Betapro- Burkholderia hypothetical GCA_001530465.1 teobacteria ubonensis protein WL11_04565 [Burkholderia ubonensis] KWI84975.1 GT4*→||||<-?||ABhydrolase→||||<-TRANSGLUTAMINASE GT4 325 WM08_23745 Betapro- Burkholderia hypothetical GCA_001534135.1 teobacteria ubonensis protein WM08_23745 [Burkholderia ubonensis] KWK82218.1 NACHT+TPR+GT4*→ NACHT+TPR+GT4 1024 WM17_17155 Betapro- Burkholderia hypothetical GCA_001533745.1 teobacteria ubonensis protein WM17_17155 [Burkholderia ubonensis] MBA3007143.1 APATPase+GT4+TPR+TPR+TPR+TPR+TPR*→ APATPase+GT4+TPR+TPR+TPR+TPR+TPR 1488 FP810_11305 Deltapro- Desulfocapsa sp. tetratricopeptide GCA_013792135.1 teobacteria repeat protein [Desulfocapsa sp.] MBA3548505.1 GT4*→ GT4 125 H0T76_18640 Deltapro- Nannocystis sp. glycosyltrans- GCA_013812955.1 teobacteria ferase [Nannocystis sp.] MBS82255.1 NACHT+GT4*→?→?→?→||||<-?<-?<-SIG+rve
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