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Vol. 34, No. 4-5, 2005
Issue release date: May 2006
Pathophysiol Haemos Thromb 2005;34:150–155
(DOI:10.1159/000092414)

Snake C-Type Lectin-Like Proteins and Platelet Receptors

Clemetson K.J. · Lu Q. · Clemetson J.M.
Theodor Kocher Institute, University of Berne, Berne, Switzerland
email Corresponding Author

Abstract

Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with α and β subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, α2β1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin α2β1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.


 goto top of outline Key Words

  • Platelets
  • C-type lectin-like proteins
  • Glycoprotein Ib
  • Glycoprotein VI
  • Collagen

 goto top of outline Abstract

Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with α and β subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, α2β1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin α2β1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.

Copyright © 2005 S. Karger AG, Basel


 goto top of outline References
  1. Chou KC: Knowledge-based model building of the tertiary structures for lectin domains of the selectin family. J Protein Chem 1996;15:161–168.
  2. Drickamer K, Taylor ME: Biology of animal lectins. Annu Rev Cell Biol 1993;9:237–264.
  3. Drickamer K: C-type lectin-like domains. Curr Opin Struct Biol 1999;9:585–590.
  4. Mizuno H, Fujimoto Z, Koizumi M, Kano H, Atoda H, Morita T: Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nat Struct Biol 1997;4:438–441.
  5. Fukuda K, Mizuno H, Atoda H, Morita T: Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers. Biochemistry 2000;39:1915–1923.
  6. Chung CH, Au LC, Huang TF: Molecular cloning and sequence analysis of aggretin, a collagen-like platelet aggregation inducer. Biochem Biophys Res Commun 1999;263:723–727.
  7. Horii K, Okuda D, Morita T, Mizuno H: Crystal structure of EMS16 in complex with the integrin alpha2-I domain. J Mol Biol 2004; 341:519–527.
  8. Fukuda K, Doggett TA, Bankston LA, Cruz MA, Diacovo TG, Liddington RC: Structural basis of von Willebrand factor activation by the snake toxin botrocetin. Structure 2002;10:943–950.
  9. Maita N, Nishio K, Nishimoto E, Matsui T, Shikamoto Y, Morita T, Sadler JE, Mizuno H: Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: insight into glycoprotein Ibα binding mechanism induced by snake venom proteins. J Biol Chem 2003;278:37777–37781.
  10. Navdaev A, Dormann D, Clemetson JM, Clemetson KJ: Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction. Blood 2001;97:2333–2341.
  11. Polgar J, Clemetson JM, Kehrel BE, Wiedemann M, Magnenat EM, Wells TN, Clemetson KJ: Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J Biol Chem 1997;272:13576–13583.
  12. Lee WH, Du XY, Lu QM, Clemetson KJ, Zhang Y: Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI. Thromb Haemost2003;90:662–671.
  13. Du XY, Clemetson JM, Navdaev A, Magnenat EM, Wells TN, Clemetson KJ: Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI. J Biol Chem 2002;277:35124–35132.
  14. Horii K, Okuda D, Morita T, Mizuno H: Crystal structure of EMS16 in complex with the integrin α2-I domain. J Mol Biol 2004;341:519–527.
  15. Kowalska MA, Tan L, Holt JC, Peng M, Karczewski J, Calvete JJ, Niewiarowski S: Alboaggregins A and B. Structure and interaction with human platelets. Thromb Haemost 1998;79:609–613.
  16. Lu QM, Navdaev A, Clemetson JM, Clemetson KJ: GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lec- tin protein from Chinese habu (Trimeresurus mucrosquamatus) venom. Thromb Haemost 2004:91:1168–1176.
  17. Dormann D, Clemetson JM, Navdaev A, Kehrel BE, Clemetson KJ: Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib. Blood 2001;97:929–936.
  18. Fukuda K, Doggett T, Laurenzi IJ, Liddington RC, Diacovo TG: The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation. Nat Struct Mol Biol 2005;12:152–159.
  19. Clemetson JM, Polgar J, Magnenat E, Wells TN, Clemetson KJ: The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcαR and the natural killer receptors. J Biol Chem 1999;274:29019–29024.
  20. Paaventhan P, Kong C, Joseph JS, Chung MC, Kolatkar PR: Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Sci 2005;14:169–175.

 goto top of outline Author Contacts

Dr. K.J. Clemetson
Theodor Kocher Institute, University of Berne
Freiestrasse 1
CH–3012 Berne (Switzerland)
Tel. +41 31 631 41 48, Fax +41 31 921 54 43, E-Mail clemetson@tki.unibe.ch


 goto top of outline Article Information

Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 0, Number of References : 20


 goto top of outline Publication Details

Pathophysiology of Haemostasis and Thrombosis

Vol. 34, No. 4-5, Year 2005 (Cover Date: May 2006)

Journal Editor: Rosing, J. (Maastricht)
ISSN: 1424–8832 (print), 1424–8840 (Online)

For additional information: http://www.karger.com/PHT


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with α and β subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, α2β1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin α2β1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.



 goto top of outline Author Contacts

Dr. K.J. Clemetson
Theodor Kocher Institute, University of Berne
Freiestrasse 1
CH–3012 Berne (Switzerland)
Tel. +41 31 631 41 48, Fax +41 31 921 54 43, E-Mail clemetson@tki.unibe.ch


 goto top of outline Article Information

Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 0, Number of References : 20


 goto top of outline Publication Details

Pathophysiology of Haemostasis and Thrombosis

Vol. 34, No. 4-5, Year 2005 (Cover Date: May 2006)

Journal Editor: Rosing, J. (Maastricht)
ISSN: 1424–8832 (print), 1424–8840 (Online)

For additional information: http://www.karger.com/PHT


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Chou KC: Knowledge-based model building of the tertiary structures for lectin domains of the selectin family. J Protein Chem 1996;15:161–168.
  2. Drickamer K, Taylor ME: Biology of animal lectins. Annu Rev Cell Biol 1993;9:237–264.
  3. Drickamer K: C-type lectin-like domains. Curr Opin Struct Biol 1999;9:585–590.
  4. Mizuno H, Fujimoto Z, Koizumi M, Kano H, Atoda H, Morita T: Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nat Struct Biol 1997;4:438–441.
  5. Fukuda K, Mizuno H, Atoda H, Morita T: Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers. Biochemistry 2000;39:1915–1923.
  6. Chung CH, Au LC, Huang TF: Molecular cloning and sequence analysis of aggretin, a collagen-like platelet aggregation inducer. Biochem Biophys Res Commun 1999;263:723–727.
  7. Horii K, Okuda D, Morita T, Mizuno H: Crystal structure of EMS16 in complex with the integrin alpha2-I domain. J Mol Biol 2004; 341:519–527.
  8. Fukuda K, Doggett TA, Bankston LA, Cruz MA, Diacovo TG, Liddington RC: Structural basis of von Willebrand factor activation by the snake toxin botrocetin. Structure 2002;10:943–950.
  9. Maita N, Nishio K, Nishimoto E, Matsui T, Shikamoto Y, Morita T, Sadler JE, Mizuno H: Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: insight into glycoprotein Ibα binding mechanism induced by snake venom proteins. J Biol Chem 2003;278:37777–37781.
  10. Navdaev A, Dormann D, Clemetson JM, Clemetson KJ: Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction. Blood 2001;97:2333–2341.
  11. Polgar J, Clemetson JM, Kehrel BE, Wiedemann M, Magnenat EM, Wells TN, Clemetson KJ: Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J Biol Chem 1997;272:13576–13583.
  12. Lee WH, Du XY, Lu QM, Clemetson KJ, Zhang Y: Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI. Thromb Haemost2003;90:662–671.
  13. Du XY, Clemetson JM, Navdaev A, Magnenat EM, Wells TN, Clemetson KJ: Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI. J Biol Chem 2002;277:35124–35132.
  14. Horii K, Okuda D, Morita T, Mizuno H: Crystal structure of EMS16 in complex with the integrin α2-I domain. J Mol Biol 2004;341:519–527.
  15. Kowalska MA, Tan L, Holt JC, Peng M, Karczewski J, Calvete JJ, Niewiarowski S: Alboaggregins A and B. Structure and interaction with human platelets. Thromb Haemost 1998;79:609–613.
  16. Lu QM, Navdaev A, Clemetson JM, Clemetson KJ: GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lec- tin protein from Chinese habu (Trimeresurus mucrosquamatus) venom. Thromb Haemost 2004:91:1168–1176.
  17. Dormann D, Clemetson JM, Navdaev A, Kehrel BE, Clemetson KJ: Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib. Blood 2001;97:929–936.
  18. Fukuda K, Doggett T, Laurenzi IJ, Liddington RC, Diacovo TG: The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation. Nat Struct Mol Biol 2005;12:152–159.
  19. Clemetson JM, Polgar J, Magnenat E, Wells TN, Clemetson KJ: The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcαR and the natural killer receptors. J Biol Chem 1999;274:29019–29024.
  20. Paaventhan P, Kong C, Joseph JS, Chung MC, Kolatkar PR: Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Sci 2005;14:169–175.