TonB-linked outer membrane protein, SusC/RagA family; This model describes a distinctive clade among the TonB-linked outer membrane proteins (OMP). Members of this family are restricted to the Bacteriodetes lineage (except for Gemmatimonas aurantiaca T-27 from the novel phylum Gemmatimonadetes) and occur in high copy numbers, with over 100 members from Bacteroides thetaiotaomicron VPI-5482 alone. Published descriptions of members of this family are available for RagA from Porphyromonas gingivalis, SusC from Bacteroides thetaiotaomicron, and OmpW from Bacteroides caccae. Members form pairs with members of the SusD/RagB family (pfam07980). Transporter complexes including these outer membrane proteins are likely to import large degradation products of proteins (e.g. RagA) or carbohydrates (e.g. SusC) as nutrients, rather than siderophores. [Transport and binding proteins, Unknown substrate]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635  341 FSIRNAGS---QPQPLILVDGKEITgEQMQrDINPDMIESISVLKDEASTAIYGDKAKHGVILITLK-GK 406
Cdd:TIGR04056 140 IWIRGISSfggNNSPLYVIDGVPRD-NGLS-DLNPEDIESISVLKDASATAIYGSRGANGVILITTKrGK 207

Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; This family contains peptidase M56, which includes zinc metalloprotease domain in MecR1 as well as BlaR1. MecR1 is a transmembrane beta-lactam sensor/signal transducer protein that regulates the expression of an altered penicillin-binding protein PBP2a, which resists inactivation by beta-lactam antibiotics, in methicillin-resistant Staphylococcus aureus (MRSA). BlaR1 regulates the inducible expression of a class A beta-lactamase that hydrolytically destroys certain ?-lactam antibiotics in MRSA. Both, MecR1 and BlaR1, are transmembrane proteins that consist of four transmembrane helices, a cytoplasmic zinc protease domain, and the soluble C-terminal extracellular sensor domain, and are highly similar in sequence and function. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. All members contain the zinc metalloprotease motif (HEXXH). Homologs of this peptidase domain are also found in a number of other bacterial genome sequences, most of which are as yet uncharacterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 100 VYLSGVLFFACRHIYSLGRLLMLLRSGE------------KEKMENGMTLVIHQQKISPFS---WMKYIVISKVDLEEDG 164
Cdd:cd07341    1 IWLAGALLLLLRLLRGLLRLRRLRRRAEpvpdslllelarRLGLRRSVRLSVSALVASPMVvglFRPVILLPEGLLEGSP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 165 RE---ILIHEAAHVRNRHSVDLLIADICIFFQWFNPASWLLKQELQNIHEYEADESVIREGVNTRQYQLLLIKKAVGTRL 241
Cdd:cd07341   81 EElraILLHELAHIRRRDLLVNLLQRLLEALFWFNPLVWLLSRRLRLERELACDEAVLAALGDKEDYAEALLRLAERRSQ 160

                        170       180
                 ....*....|....*....|....*..
gi 392701635 242 YSMANSF----NHSKLKKRITMMLKEK 264
Cdd:cd07341  161 PPPALALalagSKSLLKRRIKRILKKK 187

Outer membrane cobalamin receptor protein BtuB [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 341 FSIRNAGSQpQPLILVDGKEITGEQMQ----RDINPDMIESISVLKDEAStAIYGDKAKHGVILITLKGKDVQNVLSLSA 416
Cdd:COG4206   59 ISIRGLGSN-QTLVLIDGVPLNDPSLGgvdlSLIPPDDIERIEVLKGAAS-ALYGSDAIGGVINITTKKGKKGFKGSVSA 136

                 .
gi 392701635 417 S 417
Cdd:COG4206  137 S 137

BlaR1 peptidase M56; Production of beta-Lactamase and penicillin-binding protein 2a (which mediate staphylococcal resistance to beta-lactam antibiotics) is regulated by a signal-transducing integral membrane protein and a transcriptional repressor. The signal transducer is a fusion protein with penicillin-binding and zinc metalloprotease domains. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. homologs to this peptidase domain, which corresponds to Merops family M56, are also found in a number of other bacterial genome sequences.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635   88 AVTLSGIQILLMVYLSGVLFFACRHIYSLGRL------LMLLRSGEKEKMENGMTLVIHQQKISPFS---WMKYIVISKV 158
Cdd:pfam05569 104 LLWIVGALILLLYMIAAYLVFRQRRVRRLGSLraheldDILKEAKEDMGIKRPITISLSSNIDSPAVlglWKPRIVLPAD 183

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635  159 DLEE-DGRE---ILIHEAAHVRnRHsvDLLIADICIFFQ---WFNPASWLLKQELQNIHEYEADESVI-REGVNTR-QYQ 229
Cdd:pfam05569 184 FDTRlSGEEidyILAHELSHLK-RG--DLIINLLVAVLQclhWFNPLVHLAFRKIRIDQELACDAAVLaRLHPHERkEYG 260

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 392701635  230 LLLIKKAVGTRLYSM-----ANSFNHSKLKKRITM 259
Cdd:pfam05569 261 RTLLKLLAGPSNHIVpvacvWLAGAKSALKERIMM 295

TonB-dependent Receptor Plug Domain; The Plug domain has been shown to be an independently folding subunit of the TonB-dependent receptors. It acts as the channel gate, blocking the pore until the channel is bound by ligand. At this point it under goes conformational changes opens the channel.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 392701635  341 FSIRNAGSQpQPLILVDGKEI-TGEQMQRD---INPDMIESISVLKDeASTAIYGDKA 394
Cdd:pfam07715  48 ISIRGFGSN-RVLVLVDGVPLnSGGGGSVDlnsIDPEDIERVEVLKG-PASALYGSGA 103

TonB dependent/Ligand-Gated channels are created by a monomeric 22 strand (22,24) anti-parallel beta-barrel. Ligands apparently bind to the large extracellular loops. The N-terminal 150-200 residues form a plug from the periplasmic end of barrel. Energy (proton-motive force) and TonB-dependent conformational alteration of channel (parts of plug, and loops 7 and 8) allow passage of ligand. FepA residues 12-18 form the TonB box, which mediates the interaction with the TonB-containing inner membrane complex. TonB preferentially interacts with ligand-bound receptors. Transport thru the channel may resemble passage thru an air lock. In this model, ligand binding leads to closure of the extracellular end of pore, then a TonB-mediated signal facillitates opening of the interior side of pore, deforming the N-terminal plug and allowing passage of the ligand to the periplasm. Such a mechanism would prevent the free diffusion of small molecules thru the pore.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 341 FSIRnaGSQPQP-LILVDGKEITGEQMQRD-----INPDMIESISVLKDeASTAIYGDKAKHGVILITLKGKDVQNVLSL 414
Cdd:cd01347   41 ISIR--GFGPDRtLVLVDGLPLASSNYGRGvdlntIPPELIERVEVLKG-PSSALYGSGAIGGVVNIITKRPTDEFGGSV 117

                 ...
gi 392701635 415 SAS 417
Cdd:cd01347  118 TAG 120

Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; This family contains peptidase M56, which includes zinc metalloprotease domain in MecR1 as well as BlaR1. MecR1 is a transmembrane beta-lactam sensor/signal transducer protein that regulates the expression of an altered penicillin-binding protein PBP2a, which resists inactivation by beta-lactam antibiotics, in methicillin-resistant Staphylococcus aureus (MRSA). BlaR1 regulates the inducible expression of a class A beta-lactamase that hydrolytically destroys certain ?-lactam antibiotics in MRSA. Both, MecR1 and BlaR1, are transmembrane proteins that consist of four transmembrane helices, a cytoplasmic zinc protease domain, and the soluble C-terminal extracellular sensor domain, and are highly similar in sequence and function. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. All members contain the zinc metalloprotease motif (HEXXH). Homologs of this peptidase domain are also found in a number of other bacterial genome sequences, most of which are as yet uncharacterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 100 VYLSGVLFFACRHIYSLGRLLMLLRSGE------------KEKMENGMTLVIHQQKISPFS---WMKYIVISKVDLEEDG 164
Cdd:cd07341    1 IWLAGALLLLLRLLRGLLRLRRLRRRAEpvpdslllelarRLGLRRSVRLSVSALVASPMVvglFRPVILLPEGLLEGSP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 165 RE---ILIHEAAHVRNRHSVDLLIADICIFFQWFNPASWLLKQELQNIHEYEADESVIREGVNTRQYQLLLIKKAVGTRL 241
Cdd:cd07341   81 EElraILLHELAHIRRRDLLVNLLQRLLEALFWFNPLVWLLSRRLRLERELACDEAVLAALGDKEDYAEALLRLAERRSQ 160

                        170       180
                 ....*....|....*....|....*..
gi 392701635 242 YSMANSF----NHSKLKKRITMMLKEK 264
Cdd:cd07341  161 PPPALALalagSKSLLKRRIKRILKKK 187

Outer membrane cobalamin receptor protein BtuB [Coenzyme transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635 341 FSIRNAGSQpQPLILVDGKEITGEQMQ----RDINPDMIESISVLKDEAStAIYGDKAKHGVILITLKGKDVQNVLSLSA 416
Cdd:COG4206   59 ISIRGLGSN-QTLVLIDGVPLNDPSLGgvdlSLIPPDDIERIEVLKGAAS-ALYGSDAIGGVINITTKKGKKGFKGSVSA 136

                 .
gi 392701635 417 S 417
Cdd:COG4206  137 S 137

BlaR1 peptidase M56; Production of beta-Lactamase and penicillin-binding protein 2a (which mediate staphylococcal resistance to beta-lactam antibiotics) is regulated by a signal-transducing integral membrane protein and a transcriptional repressor. The signal transducer is a fusion protein with penicillin-binding and zinc metalloprotease domains. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. homologs to this peptidase domain, which corresponds to Merops family M56, are also found in a number of other bacterial genome sequences.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635   88 AVTLSGIQILLMVYLSGVLFFACRHIYSLGRL------LMLLRSGEKEKMENGMTLVIHQQKISPFS---WMKYIVISKV 158
Cdd:pfam05569 104 LLWIVGALILLLYMIAAYLVFRQRRVRRLGSLraheldDILKEAKEDMGIKRPITISLSSNIDSPAVlglWKPRIVLPAD 183

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392701635  159 DLEE-DGRE---ILIHEAAHVRnRHsvDLLIADICIFFQ---WFNPASWLLKQELQNIHEYEADESVI-REGVNTR-QYQ 229
Cdd:pfam05569 184 FDTRlSGEEidyILAHELSHLK-RG--DLIINLLVAVLQclhWFNPLVHLAFRKIRIDQELACDAAVLaRLHPHERkEYG 260

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 392701635  230 LLLIKKAVGTRLYSM-----ANSFNHSKLKKRITM 259
Cdd:pfam05569 261 RTLLKLLAGPSNHIVpvacvWLAGAKSALKERIMM 295

TonB-dependent outer membrane receptor, SusC/RagA subfamily, signature region; This model describes a 31-residue signature region of the SusC/RagA family of outer membrane proteins from the Bacteriodetes. While many TonB-dependent outer membrane receptors are associated with siderophore import, this family seems to include generalized nutrient receptors that may convey fairly large oligomers of protein or carbohydrate. This family occurs in high copy numbers in the most abundant species of the human gut microbiome.

                          10        20        30
                  ....*....|....*....|....*....|
gi 392701635  375 IESISVLKDEASTAIYGDKAKHGVILITLK 404
Cdd:TIGR04057   2 IESISVLKDASAAAIYGSRGANGVILITTK 31

TonB-dependent Receptor Plug Domain; The Plug domain has been shown to be an independently folding subunit of the TonB-dependent receptors. It acts as the channel gate, blocking the pore until the channel is bound by ligand. At this point it under goes conformational changes opens the channel.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 392701635  341 FSIRNAGSQpQPLILVDGKEI-TGEQMQRD---INPDMIESISVLKDeASTAIYGDKA 394
Cdd:pfam07715  48 ISIRGFGSN-RVLVLVDGVPLnSGGGGSVDlnsIDPEDIERVEVLKG-PASALYGSGA 103

Peptidase M56-like including those in BlaR1 and MecR1, integral membrane metallopeptidase; This family contains peptidase M56, which includes zinc metalloprotease domain in MecR1 as well as BlaR1. MecR1 is a transmembrane beta-lactam sensor/signal transducer protein that regulates the expression of an altered penicillin-binding protein PBP2a, which resists inactivation by beta-lactam antibiotics, in methicillin-resistant Staphylococcus aureus (MRSA). BlaR1 regulates the inducible expression of a class A beta-lactamase that hydrolytically destroys certain ?-lactam antibiotics in MRSA. Both, MecR1 and BlaR1, are transmembrane proteins that consist of four transmembrane helices, a cytoplasmic zinc protease domain, and the soluble C-terminal extracellular sensor domain, and are highly similar in sequence and function. The signal for protein expression is transmitted by site-specific proteolytic cleavage of both the transducer, which auto-activates, and the repressor, which is inactivated, unblocking gene transcription. All members contain the zinc metalloprotease motif (HEXXH). Homologs of this peptidase domain are also found in a number of other bacterial genome sequences, most of which are as yet uncharacterized.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392701635 153 IVISK--VD-LEEDGRE-ILIHEAAHVRNRHSVDLLIADICIFFQWFNPASWLLKQELQNIHEYEADESVIRE 221
Cdd:cd07326   49 IVLSTglLElLSPEELRaVLAHERAHLRRRDPLLLLLASALARALPFLPLLRRLAAAYRLLRELAADDAAARR 121

FepA family TonB-dependent siderophore receptor;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392701635 353 LILVDGKEIT----------GEQMQR-DIN---PDMIESISVLKDEAStAIYGDKAKHGVILITLK 404
Cdd:PRK13524 110 LILIDGKPVSsrnsvrygwrGERDTRgDTNwvpPEMIERIEVLRGPAA-ARYGNGAAGGVVNIITK 174