family of the cytolysin A (ClyA) family alpha pore-forming toxins (alpha-PFT) including Bacillus cereus HblB, Aeromonas hydrophila AhlB, Bacillus thuringiensis Cry6Aa and similar proteins; This family belongs to the ClyA family of alpha-PFT bacterial toxins. PFTs form the major group of virulence factors in many pathogenic bacteria and in general are critical components of the molecular offensive and defensive machinery of cells in all kingdoms of life. Bacterial PFTs facilitate the takeover of host resources by puncturing holes in the membrane. PFTs can be classified as alpha-PFTs and beta-PFTs depending on the secondary structures of their membrane component. Alpha-PFTs use a ring of amphipathic helices while beta-PFTs use a beta-barrel to construct the pore. Members of this family include the toxins: Bacillus cereus hemolysin binding component B (HblB or HBL-B) of the diarrheal enterotoxin hemolysin BL, Aeromonas hydrophila hemolytic (Ahl) component B (AhlB) of the tripartite AhlABC toxin, Vibrio cholerae cytotoxin motility associated killing factor A (MakA) cytotoxin, Xenorhabdus nematophila alpha-xenorhabdolysin (XaxA), Bacillus thuringiensis crystal 6Aa (Cry6Aa) parasporal crystal (Cry) toxin, and Bacillus cereus non-hemolytic enterotoxin (Nhe) component A (NheA) of the non-hemolytic enterotoxin Nhe, which, despite its name, is hemolytic, among others. In solution, ClyA proteins have an elongated, almost entirely alpha-helical structure, except for a short hydrophobic beta-hairpin known as the beta-tongue. Pore formation by ClyA requires circular oligomerization of the toxin by a sequential mechanism. This, in turn, concentrates the amphipathic helices in the center of the ring-like structure, forming a helical barrel that inserts into the membrane by a wedge-like mechanism. Compared with ClyA, NheA is almost entirely alpha-helical with an enlarged "head" domain, and an enlarged beta-tongue; it has been proposed that NheA could even form beta-barrel pores. Alpha-PFTs with similar structures are increasingly being found in eukaryotes, in particular as components of the immune systems of animals. This family may be distantly related to Escherichia coli alpha-PFT hemolysin E (HlyE, also known as ClyA or SheA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154  42 SSALRKIGAHSKLTQTFIDGALASPNVQLEEVPSLNTTQFLIKQDMKEWSSELYPKLILLNSKSKGFVTKFNSYYPTLK- 120
Cdd:cd22654     1 SNSIRSLGSQSPLLQAYALVILKQPNVKIEAMPSLTNHQQTAKENVREWLDEYNPKLIDLNQDMINFSQRFNNYYDKLYd 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154 121 --GFIDNGED-KEGFTDRLEVLQDMTITNQESVQRQINELTDLKLQVDKKLKNLDTDVAKTQSVLNSEgTGKIDKLKNEM 197
Cdd:cd22654    81 laGKINEDEQaKEDFLNGINKLQSQLQTIQNSMEQTSSNLNRFKTLLDADSKNFSTDAKKAIDSLSGS-NGEIAQLRTQI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154 198 LDTKKSIQNDLQQIallpgalneqglkvfqeiyslskdiiepaaqtavvaynkgkeINNAIvdaenkaeqeakEKGKSAI 277
Cdd:cd22654   160 KTINDEIQEELTKI------------------------------------------LNRPI------------EVGDGSI 185

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154 278 EIeaakkeareaiekskkGEIaaaAVTKTKEYDLMKVIDPEKIKKTYNTFaeINKLTAEQRAYLNDLEKQNQKLYDLTTK 357
Cdd:cd22654   186 NI----------------GKQ---VFTITITTATTKTVDVTSIGGLINGI--GNASDDEVKEAANKIQQKQKELVDLIKK 244

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154 358 LTVADLQKSMILFMQNDLHTFANQVDGEIELMKRYKEDLDLINNSITKLSTEVDANNTQSQ--KDTLRRLKSVTTQLEEQ 435
Cdd:cd22654   245 LSDAEIQATQLTLVEDQVNGFTELIKRQIATLENLVEDWEMLNQNMNQLQTNVNSGKIDSKllQKQLKQIKKISDELNKQ 324

                  ....
gi 1196988154 436 VYKF 439
Cdd:cd22654   325 TKQF 328

family of the cytolysin A (ClyA) family alpha pore-forming toxins (alpha-PFT) including Bacillus cereus HblB, Aeromonas hydrophila AhlB, Bacillus thuringiensis Cry6Aa and similar proteins; This family belongs to the ClyA family of alpha-PFT bacterial toxins. PFTs form the major group of virulence factors in many pathogenic bacteria and in general are critical components of the molecular offensive and defensive machinery of cells in all kingdoms of life. Bacterial PFTs facilitate the takeover of host resources by puncturing holes in the membrane. PFTs can be classified as alpha-PFTs and beta-PFTs depending on the secondary structures of their membrane component. Alpha-PFTs use a ring of amphipathic helices while beta-PFTs use a beta-barrel to construct the pore. Members of this family include the toxins: Bacillus cereus hemolysin binding component B (HblB or HBL-B) of the diarrheal enterotoxin hemolysin BL, Aeromonas hydrophila hemolytic (Ahl) component B (AhlB) of the tripartite AhlABC toxin, Vibrio cholerae cytotoxin motility associated killing factor A (MakA) cytotoxin, Xenorhabdus nematophila alpha-xenorhabdolysin (XaxA), Bacillus thuringiensis crystal 6Aa (Cry6Aa) parasporal crystal (Cry) toxin, and Bacillus cereus non-hemolytic enterotoxin (Nhe) component A (NheA) of the non-hemolytic enterotoxin Nhe, which, despite its name, is hemolytic, among others. In solution, ClyA proteins have an elongated, almost entirely alpha-helical structure, except for a short hydrophobic beta-hairpin known as the beta-tongue. Pore formation by ClyA requires circular oligomerization of the toxin by a sequential mechanism. This, in turn, concentrates the amphipathic helices in the center of the ring-like structure, forming a helical barrel that inserts into the membrane by a wedge-like mechanism. Compared with ClyA, NheA is almost entirely alpha-helical with an enlarged "head" domain, and an enlarged beta-tongue; it has been proposed that NheA could even form beta-barrel pores. Alpha-PFTs with similar structures are increasingly being found in eukaryotes, in particular as components of the immune systems of animals. This family may be distantly related to Escherichia coli alpha-PFT hemolysin E (HlyE, also known as ClyA or SheA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154  45 LRKIGAHSKLTQTFIDGALASPNVQ---LEEVPSLNTTQFLIKQDMKEWSSELYPKLILLNSKSKGFVTKFNSYYPTLKG 121
Cdd:cd21116     1 LADLGAASALVQAYVTAILNQPNINlipLDLLPSLNTHQALARAHALEWLNEIKPKLLSLPNDIIGYNNTFQSYYPDLIE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1196988154 122 FID-----NGEDKEGFTDRLEVLQDMTITNQESVQRQINELTDLKLQVDKKLKNLDTDVAKTQS 180
Cdd:cd21116    81 LADnlikgDQGAKQQLLQGLEALQSQVTKKQTSVTSFINELTTFKNDLDDDSRNLQTDATKAQA 144

family of the cytolysin A (ClyA) family alpha pore-forming toxins (alpha-PFT) including Bacillus cereus HblB, Aeromonas hydrophila AhlB, Bacillus thuringiensis Cry6Aa and similar proteins; This family belongs to the ClyA family of alpha-PFT bacterial toxins. PFTs form the major group of virulence factors in many pathogenic bacteria and in general are critical components of the molecular offensive and defensive machinery of cells in all kingdoms of life. Bacterial PFTs facilitate the takeover of host resources by puncturing holes in the membrane. PFTs can be classified as alpha-PFTs and beta-PFTs depending on the secondary structures of their membrane component. Alpha-PFTs use a ring of amphipathic helices while beta-PFTs use a beta-barrel to construct the pore. Members of this family include the toxins: Bacillus cereus hemolysin binding component B (HblB or HBL-B) of the diarrheal enterotoxin hemolysin BL, Aeromonas hydrophila hemolytic (Ahl) component B (AhlB) of the tripartite AhlABC toxin, Vibrio cholerae cytotoxin motility associated killing factor A (MakA) cytotoxin, Xenorhabdus nematophila alpha-xenorhabdolysin (XaxA), Bacillus thuringiensis crystal 6Aa (Cry6Aa) parasporal crystal (Cry) toxin, and Bacillus cereus non-hemolytic enterotoxin (Nhe) component A (NheA) of the non-hemolytic enterotoxin Nhe, which, despite its name, is hemolytic, among others. In solution, ClyA proteins have an elongated, almost entirely alpha-helical structure, except for a short hydrophobic beta-hairpin known as the beta-tongue. Pore formation by ClyA requires circular oligomerization of the toxin by a sequential mechanism. This, in turn, concentrates the amphipathic helices in the center of the ring-like structure, forming a helical barrel that inserts into the membrane by a wedge-like mechanism. Compared with ClyA, NheA is almost entirely alpha-helical with an enlarged "head" domain, and an enlarged beta-tongue; it has been proposed that NheA could even form beta-barrel pores. Alpha-PFTs with similar structures are increasingly being found in eukaryotes, in particular as components of the immune systems of animals. This family may be distantly related to Escherichia coli alpha-PFT hemolysin E (HlyE, also known as ClyA or SheA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154  45 LRKIGAHSKLTQTFIDGALASPNVQ---LEEVPSLNTTQFLIKQDMKEWSSELYPKLILLNSKSKGFVTKFNSYYPTLKG 121
Cdd:cd21116     1 LADLGAASALVQAYVTAILNQPNINlipLDLLPSLNTHQALARAHALEWLNEIKPKLLSLPNDIIGYNNTFQSYYPDLIE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1196988154 122 FID-----NGEDKEGFTDRLEVLQDMTITNQESVQRQINELTDLKLQVDKKLKNLDTDVAKTQS 180
Cdd:cd21116    81 LADnlikgDQGAKQQLLQGLEALQSQVTKKQTSVTSFINELTTFKNDLDDDSRNLQTDATKAQA 144

Bacillus cereus hemolysin binding component B (HblB), and similar proteins; This model includes Bacillus cereus hemolysin binding component B (HblB or HBL-B) of the diarrheal enterotoxin hemolysin BL (HBL), and is a member of the cytolysin A (ClyA) family of alpha pore-forming toxins (alpha-PFTs). HBL is composed of three distinct protein components, B, L1, and L2, which together possess hemolytic, cytotoxic, dermonecrotic, and vascular permeability activities in B. cereus. Although all three HBL components can individually bind to the membrane, it requires the three components to form a complex to form a pore. Structure of HblB shows an elongated, almost entirely alpha-helical protein, except for a short hydrophobic beta-hairpin known as the beta-tongue. HBL from Bacillus toyonensis BV-17 (a strain isolated from feces samples of healthy donors) has antitumor activity both in vitro and in vivo and may have potential as a treatment for colon cancer. For B. toyonesis HBL, combining HBL-B and HBL-L2 had no cytotoxicity but combining HBL-B and HBL-L1 does.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1196988154  63 LASPNVQLEEVPS--------LNTTQFLIKQDMKEWSSELYPKLILLNSKSKGFVTKFNSYYPTLKGFIDNGeDKEGFTD 134
Cdd:cd22653    23 LKQPDINLSGLISidgdlkkkIIQHQETARKNANYWLDTLKPQIIKTNQNIINYNTQFQNYYDTLVDAIDKK-DKETLKE 101

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1196988154 135 RLEVLQDMTITNQESVQRQINELTDLKLQVDKKLKNLDTDVAKTQS 180
Cdd:cd22653   102 GLTDLYKDISENKKEVDQLIKDLKKFRDKLSTDTQNFKNDVNQLTS 147