Protein Science
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Olson, R.
Right arrow Articles by Gouaux, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olson, R.
Right arrow Articles by Gouaux, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Protein Science (2003), 12:379-383.
Copyright © 2003 The Protein Society

FOR THE RECORD

Vibrio cholerae cytolysin is composed of an {alpha}-hemolysin-like core

Rich Olson1 and Eric Gouaux1,2

1 Department of Biochemistry and Molecular Biophysics
2 Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA

Reprint requests to: Eric Gouaux, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; e-mail: jeg52{at}columbia.edu; fax: (212) 305-8174.

(RECEIVED September 9, 2002; FINAL REVISION October 28, 2002; ACCEPTED October 28, 2002)

Article and publication are at http://www.proteinscience.org/cgi/doi/10.1110/ps.0231703.


   Abstract
TOP
 Abstract
Introduction
 Cytolytic domain
 Stem region
 Ricin-like domain
 Conclusions
 Note added in proof
 References
 
The enteric pathogen Vibrio cholerae secretes a water-soluble 80-kD cytolysin, Vibrio cholerae cytolysin (VCC) that assembles into pentameric channels following proteolytic activation by exogenous proteases. Until now, VCC has been placed in a unique class of pore-forming toxins, distinct from paradigms such as Staphyloccal {alpha}-hemolysin. However, as reported here, amino acid sequence analysis and three-dimensional structure modeling indicate that the core component of the VCC toxin is related in sequence and structure to a family of hemolysins from Staphylococcus aureus that include leukocidin F and {alpha}-hemolysin. Furthermore, our analysis has identified the channel-forming region of VCC and a potential lipid head-group binding site, and suggests a conserved mechanism of assembly and lysis. An additional domain in the VCC toxin is related to plant lectins, conferring additional target cell specificity to the toxin.

Keywords: {alpha}-hemolysin; cytolysin; lectin; leukocidin; pore-forming bacterial toxins; ricin; Staphylococcus aureus; Vibrio cholerae

Abbreviations: VCC, Vibrio cholerae cytolysin • {alpha}HL, {alpha}-hemolysin • LukF, leukocidin F component


   Introduction
TOP
 Abstract
 Introduction
Cytolytic domain
 Stem region
 Ricin-like domain
 Conclusions
 Note added in proof
 References
 
Many pathogenic bacteria secrete pore-forming toxins that bind and assemble on target cell membranes, forming lytic, transmembrane ion channels (Gouaux 1997). A subset of these toxins employ ß-barrels to span the bilayer, where the barrel is composed of strands contributed by protomers arranged around a rotational axis of symmetry (Heuck et al. 2001; Menestrina et al. 2001). High-resolution structures of the water-soluble, monomeric leukocidin F (LukF; Olson et al. 1999; Pedelacq et al. 1999) and the detergent-soluble, heptameric channel of {alpha}-hemolysin ({alpha}HL; Song et al. 1996) from Staphylococcus aureus define the initial and final steps on the assembly pathway, illuminating the conformational rearrangements that occur upon pore formation. Although the sequence identity between {alpha}HL and LukF is low (~30%), the structural cores of the proteins are superimposable, as previously predicted from sequence analysis (Gouaux et al. 1997).

Vibrio cholerae cytolysin (VCC) is an important pore-forming toxin and, until now, has been classified as functionally and structurally distinct from the S. aureus toxins described above. For example, VCC exhibits specificity for membranes containing cholesterol and ceramides (Zitzer et al. 1999) and contains a prodomain that is required for folding and must be cleaved to produce mature toxin (Nagamune et al. 1997). In contrast, {alpha}HL and LukF are most active at membranes that contain phosphatidylcholine; they each contain a specific binding site for phosphocholine (Tomita and Kamio 1997), and they do not have a prodomain. Furthermore, the 65-kD mature VCC protein assembles to form pentameric channels (Zitzer et al. 1999), whereas the {alpha}HL 33-kD protomer assembles to a homoheptamer, and LukF (34 kD), together with LukS, forms a heteroheptamer (Sugawara-Tomita et al. 2002) or a heterooctamer (Miles et al. 2002). On the basis of functional properties, differences in protomer molecular mass and oligomer subunit stoichiometry, and apparent absence of amino acid sequence homology, the VCC toxin appears to be unrelated in structure and mechanism to LukF and {alpha}HL.

To determine the extent to which VCC may be related in amino acid sequence, three-dimensional structure, and biological function to the {alpha}HL family of pore-forming toxins from Staphylococcus aureus, we employed {Psi}-BLAST at the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/) using the complete VCC protein sequence (NCBI accession number NP_232618) as a search probe. After several rounds of iterative searching, the LukF and {alpha}HL sequences were located with E-values of 10-63 and 10-49, respectively. This analysis clearly revealed that VCC contains a central region of ~250 amino acid residues that is related to the Aerolysin/Hemolysin/Leukocidin family of pore-forming toxins (Bateman et al. 2002), which we hereafter call the cytolytic domain (Fig. 1Go). A closer examination of the search results indicated that VCC is more closely related to the Staphylococcal {alpha}-hemolysin and leukocidin toxins than the aerolysin protein from Aeromonas hydrophila, although Aeromonas has a separate VCC-like toxin. We also discovered that following the cytolytic domain, VCC has a ricin-like domain (Schultz et al. 1998) spanning residues R484 to T600. After the ricin-like domain there are ~140 amino acids of unknown function or structure that can be proteolytically removed without impairing the function of the toxin (Ikigai et al. 1999; Zitzer et al. 1999), and that are missing in related cytolysins from Vibrio vulnificus (Yamamoto et al. 1990), Aeromonas hydrophila (Hirono and Aoki 1991; Wong et al. 1998), and Aeromonas salmonicida (Hirono and Aoki 1993).



View larger version (12K):
[in this window]
[in a new window]
  		Figure 1. Domain outline of the Vibrio cholerae cytolysin gene, showing the location of the {alpha}-hemolysin-like cytolytic domain in green.

 
Careful analysis of the sequence alignments among VCC, {alpha}HL, and LukF indicates that these toxins have a common cytolytic core with a similar overall fold. We have outlined the putative membrane-crossing region and suggest that the VCC pore is an antiparallel ß-barrel. We also hypothesize that the ricin-like domain confers the carbohydrate-binding activity upon VCC. Our new observations define the architecture of the VCC protein, identify the critical pore-forming residues, and suggest that VCC and the Staphylococcus aureus toxins share a common mechanism of pore formation.


   Cytolytic domain
TOP
 Abstract
 Introduction
 Cytolytic domain
Stem region
 Ricin-like domain
 Conclusions
 Note added in proof
 References
 
The cytolytic cores of VCC, {alpha}HL, and LukF were aligned using the ClustalW program (Thompson et al. 1994), as illustrated in Figure 2Go. The first 47 residues of {alpha}HL and 46 residues of LukF did not show significant similarity to VCC and were excluded from the alignment. The sequence identity values between VCC and {alpha}HL and VCC and LukF were 16.5% and 12.9%, respectively, with 19 out of 236 residues conserved in all three proteins. Sequence similarity was ~25% between VCC and each of the S. aureus toxins, and ~45% between {alpha}HL and LukF.



View larger version (55K):
[in this window]
[in a new window]
  		Figure 2. Sequence alignment of the related domains of LukF, {alpha}HL, and VCC. Hydrophobic residues (F, I, L, V, W, Y) identical or similar in all three sequences are marked by magenta and green circles, respectively. The secondary structure of LukF from the crystal structure is illustrated above the sequences using the same coloring scheme as in Figure 3Go. The alignment was generated with ClustalW version 1.74 and displayed using Boxshade. Residues identical in two or three sequences are boxed in black, and similar residues are in gray. Green arrows designate alternating hydrophobic residues that could potentially contact the membrane.

 
Although the level of sequence identity between VCC and {alpha}HL/LukF is low, a close examination of the alignment, in light of the {alpha}HL and LukF structures, provides substantiating evidence for a similar fold, and suggests a common architecture for the transmembrane pore. Indeed, we see that hydrophobic and aromatic residues occupy key positions in the protein core (Chen and Stites 2001). There are five strictly conserved aromatics (VCC numbering: Y338, W367, Y438, Y445, W475) with six additional aromatics conservatively substituted (VCC numbering: Y260, Y279, F313, W343, Y454, F471). When mapped onto the LukF structure, most of these residues are located in the core of the ß-sandwich and rim domains (Fig. 3Go). An exception is W367 (LukF W177), which is solvent-exposed and forms a lipid head-group binding pocket in both {alpha}HL and LukF, and is found in all three sequences, thus identifying a likely lipid-head group binding site in VCC. A number of nonaromatic hydrophobic residues scattered throughout the VCC sequence are either identical or conservatively replaced in the three proteins: L251, I292, I353, I398, V407, I434, V447, and V473. On the basis of these sequence and structure relationships, we propose that the main core (ß-sandwich and rim) of the VCC cytolytic domain shares structural homology with the ß-sandwich and rim domains of the {alpha}HL and LukF toxins from S. aureus.



View larger version (53K):
[in this window]
[in a new window]
  		Figure 3. Ribbon representation of the LukF crystal structure showing conserved aromatic residues. Magenta residues are identical in all three proteins, and green residues are aromatic (F, W, Y). The amino latch (pink) and first two ß-strands (gray) do not appear to be present in VCC and were not included in the alignment in Figure 2Go.

 

   Stem region
TOP
 Abstract
 Introduction
 Cytolytic domain
 Stem region
Ricin-like domain
 Conclusions
 Note added in proof
 References
 
Using the alignment shown in Figure 2Go, we can pinpoint the stem or pore-forming region of VCC. The stem is flanked by highly conserved residues in the triangle region, is glycine-rich, and contains alternating polar and nonpolar residues. Residues in the triangle and stem of {alpha}HL make important contacts between protomers in the oligomeric state, and specific mutations in this region arrest {alpha}HL in various stages of heptamer assembly (Walker and Bayley 1995). A key proline residue (P102 in LukF) adopts a cis-peptide bond in the {alpha}HL and LukF structures, is located near a hinge point in the triangle, and is present in VCC (Olson et al. 1999).

Although the triangle region is extremely sensitive to mutations, the stem has been removed (Cheley et al. 1997), replaced (Gu et al. 2000), and even reversed (Cheley et al. 1999) without substantially affecting assembly of the {alpha}HL heptamer. In the LukF structure, the stem is folded into a three-strand ß-sheet that packs against a hydrophobic patch on the ß-sandwich domain. In the {alpha}HL heptamer, the stem is unfurled and each protomer contributes two strands to a 14-strand ß-barrel. The stem must be flexible so that it can undergo these dramatic conformational changes, and the stem has an abundance of glycine residues: eight in {alpha}HL, seven in LukF, and six in VCC.

Like other ß-barrel membrane proteins, a ring of aromatic residues is found near the apparent membrane-aqueous interface in {alpha}HL and LukF at positions Y117 and F119 (LukF). Although these residues are not identical in VCC, the phenylalanine and leucine (F313 and L315 in VCC) residues are conservative substitutions. LukF residues Y117 and F119, along with F139 (isoleucine in {alpha}HL and leucine in VCC), contact hydrophobic residues in the amino-latch in the water-soluble state (Olson et al. 1999), and may help coordinate stem unfolding with latch movement during assembly of the channel.

A hallmark of ß-barrel membrane proteins is the alternating pattern of hydrophilic and hydrophobic residues that contact the lumen of the channel and lipid moiety, respectively (Schulz 2000). This pattern is clear in the stem domains of LukF and {alpha}HL, even though the sequence identity is low, and is also evident in the stem of VCC, reinforcing our hypothesis that this region forms a transmembrane ß-barrel.

Interestingly, the putative membrane-spanning region of VCC is five residues shorter than the corresponding region of {alpha}HL, and three residues shorter than the equivalent segment of LukF. The shorter transmembrane ß-strands in VCC may be explained by VCC having a shorter assembled stem. However, the shorter length of the VCC ß-strands may also be due to the fact the VCC barrel is probably pentameric (Zitzer et al. 1999), and thus has a smaller diameter (Chothia and Murzin 1993), requiring shorter ß-strands. A smaller ß-barrel for the assembled VCC toxin is also consistent with its lower single-channel conductance (Menzl et al. 1996; Miles et al. 2001), relative to the larger barrels of {alpha}HL and leukocidin.


   Ricin-like domain
TOP
 Abstract
 Introduction
 Cytolytic domain
 Stem region
 Ricin-like domain
Conclusions
 Note added in proof
 References
 
Ricin-like lectin domains are found in many A-B type plant toxins and participate in binding ß-D-galactopyranoside molecules on the surface of cells (Olsnes and Kozlov 2001). Structures have been determined for several plant lectins with a portion of the B-subunit forming a ß-trefoil structure with three binding sites thought to have arisen from ancestral gene duplication (Rutenber et al. 1987). Most members of this family have either two or three conserved disulfide bonds, as well as three QxW motifs ({alpha}, ß, and {gamma}) around a pseudo-threefold axis that marks the carbohydrate binding sites.

The presence of a QxW motif in VCC was suggested earlier (Hazes 1996) although the carbohydrate binding capability was questioned due to low sequence homology within these domains. The carbohydrate binding ability has since been demonstrated (Saha and Banerjee 1997; Zhang et al. 1999), and the ricin-like domain is the likely site of binding. An alignment using ClustalW was performed with VCC and the lectin domains from ricin and abrin-a (Fig. 4AGo). Although the sequence identity is low (17.5%) between VCC and abrin-a, and 19.8% between VCC and ricin, there is conservation of four cysteines that form disulfide bonds in the ricin family.



View larger version (28K):
[in this window]
[in a new window]
  		Figure 4. Sequence alignment of the lectin domains of abrin-a, ricin (b-domain), and VCC. (A) Coloring of conserved residues follows the same scheme as in Figure 2Go. Note the four cysteines, which are predicted to form two disulfide bonds. The QxW domains are boxed in cyan. The secondary structure shown in red denotes the two conserved domains, and that in blue outlines the less well-conserved domain. (B) Crystal structure of the lectin domain of abrin-a (b-chain). Identical and similar hydrophobic residues are shown in magenta and in green, respectively. Conserved disulfide bonds are colored yellow. The coloring of the secondary structure is the same as that in (A).

 
As was the case with the cytolytic domains, several hydrophobic residues located in the hydrophobic core are conserved in all three proteins (Fig. 4BGo). These include F520 (in VCC), W557, W559, Y570, and Y587. Also conserved in VCC were two of the three QxW repeats, suggesting that VCC might possess up to two carbohydrate binding sites. Although most ß-trefoil lectins have three QxW repeats, many have lost activity in one or more of these sites (Notenboom et al. 2002), and it is not clear whether both repeats are able to bind sugars in VCC.

Neither {alpha}-HL nor LukF contain a lectin domain, reflecting their difference in cellular targets. The C-terminus of LukF is on the side opposite the stem domain, and attaching the lectin domain to the C-terminus of the cytolysin would not interfere with binding of the rim to the membrane (see Fig. 3Go), or with assembly of the channel. The last 15-kD domain in VCC may make additional membrane contacts, augmenting toxin specificity.


   Conclusions
TOP
 Abstract
 Introduction
 Cytolytic domain
 Stem region
 Ricin-like domain
 Conclusions
Note added in proof
 References
 
We have demonstrated that Vibrio cholerae cytolysin is related to {alpha}HL and LukF in amino acid sequence and almost certainly in three-dimensional structure, and thus may utilize a common mechanism for cell lysis. The lectin domain provides a precise mechanism by which the toxin may target specific cells. Sequence homology with conserved families account for the majority of the VCC polypeptide, leaving only the 15-kD C-terminal tail with unknown function and structure.


   Note added in proof
TOP
 Abstract
 Introduction
 Cytolytic domain
 Stem region
 Ricin-like domain
 Conclusions
 Note added in proof
References
 
While this manuscript was in press, Harris et al. ( 2002 J. Struct. Biol. 139: 122–135[CrossRef][Medline]) reported that the assembled VCC oligomer is a heptamer, like the {alpha}-HL heptamer, thus suggesting that the transmembrane domain of the VCC oligomer is a 14-strand ß-barrel.


   Acknowledgments
 
We thank Michelle Montoya for her help in preparing this manuscript, and the NIH for financial support. R.O. acknowledges support from the NIH Training Program in Molecular Biophysics. E.G. is an assistant investigator with the Howard Hughes Medical Institute.

The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.


   References
TOP
 Abstract
 Introduction
 Cytolytic domain
 Stem region
 Ricin-like domain
 Conclusions
 Note added in proof
 References
 
Bateman, A., Birney, E., Cerruti, L., Durbin, R., Etwiller, L., Eddy, S.R., Griffiths-Jones, S., Howe, K.L., Marshall, M., and Sonnhammer, E.L. 2002. The Pfam protein families database. Nucleic Acids Res. 30: 276–280.[Abstract/Free Full Text]

Cheley, S., Malghani, M.S., Song, L., Hobaugh, M., Gouaux, J.E., Yang, J., and Bayley, H. 1997. Spontaneous oligomerization of a staphylococcal {alpha}-hemolysin conformationally constrained by removal of residues that form the transmembrane ß-barrel. Protein Eng. 10: 1433–1443.[Abstract/Free Full Text]

Cheley, S., Braha, O., Lu, X., Conlan, S., and Bayley, H. 1999. A functional protein pore with a ‘retro’ transmembrane domain. Protein Sci. 8: 1257–1267.[Abstract]

Chen, J. and Stites, W.E. 2001. Packing is a key selection factor in the evolution of protein hydrophobic cores. Biochemistry 40: 15280–15289.[CrossRef][Medline]

Chothia, C. and Murzin, A.G. 1993. New folds for all-ß proteins. Structure 1: 217–222.[Medline]

Gouaux, E. 1997. Channel-forming toxins: Tales of transformation. Curr. Opin. Struct. Biol. 7: 566–573.[CrossRef][Medline]

Gouaux, E., Hobaugh, M., and Song, L. 1997. {alpha}-Hemolysin, {gamma}-hemolysin, and leukocidin from Staphylococcus aureus: Distant in sequence but similar in structure. Protein Sci. 6: 2631–2635.[Abstract]

Gu, L.Q., Dalla Serra, M., Vincent, J.B., Vigh, G., Cheley, S., Braha, O., and Bayley, H. 2000. Reversal of charge selectivity in transmembrane protein pores by using noncovalent molecular adapters. Proc. Natl. Acad. Sci. 97: 3959–3964.[Abstract/Free Full Text]

Hazes, B. 1996. The (QxW)3 domain: A flexible lectin scaffold. Protein Sci. 5: 1490–1501.[Abstract]

Heuck, A.P., Tweten, R.K., and Johnson, A.E. 2001. ß-Barrel pore-forming toxins: Intriguing dimorphic proteins. Biochemistry 40: 9065–9073.[CrossRef][Medline]

Hirono, I. and Aoki, T. 1991. Nucleotide sequence and expression of an extracellular hemolysin gene of Aeromonas hydrophila. Microb. Pathog. 11: 189–197.[CrossRef][Medline]

———. 1993. Cloning and characterization of three hemolysin genes from Aeromonas salmonicida. Microb. Pathog. 15: 269–282.[CrossRef][Medline]

Ikigai, H., Ono, T., Nakae, T., Otsuru, H., and Shimamura, T. 1999. Two forms of Vibrio cholerae O1 El Tor hemolysin derived from identical precursor protein. Biochim. Biophys. Acta 1415: 297–305.[Medline]

Menestrina, G., Serra, M.D., and Prevost, G. 2001. Mode of action of ß-barrel pore-forming toxins of the staphylococcal {alpha}-hemolysin family. Toxicon 39: 1661–1672.[Medline]

Menzl, K., Maier, E., Chakraborty, T., and Benz, R. 1996. HlyA hemolysin of Vibrio cholerae O1 biotype E1 Tor. Identification of the hemolytic complex and evidence for the formation of anion-selective ion-permeable channels. Eur. J. Biochem. 240: 646–654.[Medline]

Miles, G., Cheley, S., Braha, O., and Bayley, H. 2001. The staphylococcal leukocidin bicomponent toxin forms large ionic channels. Biochemistry 40: 8514–8522.[CrossRef][Medline]

Miles, G., Movileanu, L., and Bayley, H. 2002. Subunit composition of a bicomponent toxin: Staphylococcal leukocidin forms an octameric transmembrane pore. Protein Sci. 11: 894–902.[Abstract/Free Full Text]

Nagamune, K., Yamamoto, K., and Honda, T. 1997. Intramolecular chaperone activity of the proregion of Vibrio cholerae El Tor cytolysin. J. Biol. Chem. 272: 1338–1343.[Abstract/Free Full Text]

Notenboom, V., Boraston, A.B., Williams, S.J., Kilburn, D.G., and Rose, D.R. 2002. High-resolution crystal structures of the lectin-like xylan binding domain from Streptomyces lividans xylanase 10A with bound substrates reveal a novel mode of xylan binding. Biochemistry 41: 4246–4254.[CrossRef][Medline]

Olsnes, S. and Kozlov, J.V. 2001. Ricin. Toxicon 39: 1723–1728.[Medline]

Olson, R., Nariya, H., Yokota, K., Kamio, Y., and Gouaux, E. 1999. Crystal structure of staphylococcal LukF delineates conformational changes accompanying formation of a transmembrane channel. Nat. Struct. Biol. 6: 134–140.[CrossRef][Medline]

Pedelacq, J.D., Maveyraud, L., Prevost, G., Baba-Moussa, L., Gonzalez, A., Courcelle, E., Shepard, W., Monteil, H., Samama, J.P., and Mourey, L. 1999. The structure of a Staphylococcus aureus leucocidin component (LukF-PV) reveals the fold of the water-soluble species of a family of transmembrane pore-forming toxins. Structure Fold. Des. 7: 277–287.[Medline]

Rutenber, E., Ready, M., and Robertus, J.D. 1987. Structure and evolution of ricin B chain. Nature 326: 624–626.[CrossRef][Medline]

Saha, N. and Banerjee, K.K. 1997. Carbohydrate-mediated regulation of interaction of Vibrio cholerae hemolysin with erythrocyte and phospholipid vesicle. J. Biol. Chem. 272: 162–167.[Abstract/Free Full Text]

Schultz, J., Milpetz, F., Bork, P., and Ponting, C.P. 1998. SMART, a simple modular architecture research tool: Identification of signaling domains. Proc. Natl. Acad. Sci. 95: 5857–5864.[Abstract/Free Full Text]

Schulz, G.E. 2000. ß-Barrel membrane proteins. Curr. Opin. Struct. Biol. 10: 443–447.[CrossRef][Medline]

Song, L., Hobaugh, M.R., Shustak, C., Cheley, S., Bayley, H., and Gouaux, J.E. 1996. Structure of staphylococcal {alpha}-hemolysin, a heptameric transmembrane pore. Science 274: 1859–1866.[Abstract/Free Full Text]

Sugawara-Tomita, N., Tomita, T., and Kamio, Y. 2002. Stochastic assembly of two-component staphylococcal {gamma}-hemolysin into heteroheptameric transmembrane pores with alternate subunit arrangements in ratios of 3:4 and 4:3. J. Bacteriol. 184: 4747–4756.[Abstract/Free Full Text]

Thompson, J.D., Higgins, D.G., and Gibson, T.J. 1994. ClustalW: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22: 4673–4680.[Abstract/Free Full Text]

Tomita, T. and Kamio, Y. 1997. Molecular biology of the pore-forming cytolysins from Staphylococcus aureus, {alpha}- and {gamma}-hemolysins and leukocidin. Biosci. Biotechnol. Biochem. 61: 565–572.[Medline]

Walker, B., and Bayley, H. 1995. Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal {alpha}-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification. J. Biol. Chem. 270: 23065–23071.[Abstract/Free Full Text]

Wong, C.Y., Heuzenroeder, M.W., and Flower, R.L. 1998. Inactivation of two haemolytic toxin genes in Aeromonas hydrophila attenuates virulence in a suckling mouse model. Microbiology 144: 291–298.[Abstract]

Yamamoto, K., Wright, A.C., Kaper, J.B., and Morris, Jr., J.G., 1990. The cytolysin gene of Vibrio vulnificus: Sequence and relationship to the Vibrio cholerae E1 Tor hemolysin gene. Infect. Immun. 58: 2706–2709.[Abstract/Free Full Text]

Zhang, D., Takahashi, J., Seno, T., Tani, Y., and Honda, T. 1999. Analysis of receptor for Vibrio cholerae El tor hemolysin with a monoclonal antibody that recognizes glycophorin B of human erythrocyte membrane. Infect. Immun. 67: 5332–5337.[Abstract/Free Full Text]

Zitzer, A., Zitzer, O., Bhakdi, S., and Palmer, M. 1999. Oligomerization of Vibrio cholerae cytolysin yields a pentameric pore and has a dual specificity for cholesterol and sphingolipids in the target membrane. J. Biol. Chem. 274: 1375–1380.[Abstract/Free Full Text]


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. Valeva, I. Walev, S. Weis, F. Boukhallouk, T. M. Wassenaar, K. Endres, F. Fahrenholz, S. Bhakdi, and A. Zitzer
A Cellular Metalloproteinase Activates Vibrio cholerae Pro-cytolysin
J. Biol. Chem., June 11, 2004; 279(24): 25143 - 25148.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
S. Galdiero and E. Gouaux
High resolution crystallographic studies of {alpha}-hemolysin-phospholipid complexes define heptamer-lipid head group interactions: Implication for understanding protein-lipid interactions
Protein Sci., June 1, 2004; 13(6): 1503 - 1511.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Chattopadhyay and K. K. Banerjee
Unfolding of Vibrio cholerae Hemolysin Induces Oligomerization of the Toxin Monomer
J. Biol. Chem., October 3, 2003; 278(40): 38470 - 38475.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Olson, R.
Right arrow Articles by Gouaux, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olson, R.
Right arrow Articles by Gouaux, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS