Table Of ContentMoLECUlAR
BIOLOGY
INTELLIGENCE
UNIT
PROTEIN TOXIN
STRUCTURE
Michael W Parker, D.Phil.
St. Vincent's Institute of Medical Research
Melbourne, Australia
Springer-Verlag
RG.
Berlin Heidelberg GmbH LANDES CoMPANY
AUSTIN
MOLECULAR BIOLOGY INTELLIGENCE UNIT
PROTEIN TOXIN STRUCTURE
R.G. LANDES COMPANY
Austin, Texas, U.S.A.
International Copyright © 1996 Springer-Verlag Berlin Heidelberg
Originally published by Springer-Verlag, Heidelberg, Germany in 1996
Softcover reprint of the hardcover lst edition 1996
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'Springer
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Library of Congress Cataloging-in-Publication Data
Protein toxin structure I [edited by} Michael W. Parker.
p. em. -(Molecular biology intelligence unit)
Includes bibliographical references and index.
ISBN 978-3-662-22354-3 ISBN 978-3-662-22352-9 (eBook)
DOI 10.1007/978-3-662-22352-9
1. Toxins-Structure-activity relationships. I. Parker, Michael W., 1959-. II. Series.
QP631.P76 1996
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r,======CONTENTS====~
1. Introduction ............................................................................... 1
joseph E. Alouf
2. Insights into Membrane Insertion
Ba~ed on Studies of Colicins ....................................................... 5
Ingrid R. Vetter, Michael W. Parker, Franc Pattus
and Demetrius Tsernoglou
Domain Organization of the Colicins ................................................... 6
Receptor Binding .................................................................................. 8
Translocation ........................................................................................ 8
The Bacteriocidal Effect ........................................................................ 9
Structure of the Pore-Forming Domain .............................................. 10
Channel Formation ............................................................................. 14
Structure of the Receptor Binding and Translocation Domain ............ 16
Binding and Transport of Colicin N ................................................... 17
Immunity Proteins .............................................................................. 18
Conclusions ........................................................................................ 19
3. A Structure-Based Model of Diphtheria Toxin Action .............. 25
David Eisenberg, Charles E. Bell, Melanie J Bennett, R. john Collier,
Michael P. Schlunegger, Boyd A. Steere and Manfred S. Weiss
Molecular Introduction ....................................................................... 27
Oligomeric Forms ofDT .................................................................... 33
Mechanism for Intoxication by DT .................................................... 37
The Mechanism of Action of the C Domain ....................................... 39
4. Insecticidal 8-Endoto:xins from Bacillus thuringiensis ................ 49
jade Li
Cry 8-Endotoxin Structures ................................................................. 51
Structure of the Mosquitocidal and Cytolytic Toxin CytB .................. 64
Concluding Remarks .......................................................................... 69
5. Structure and Assembly of the Channel-Forming
Aerom onas Toxin Aero lysin ...................................................... 79
Michael W. Parker, J Thomas Buckley, F. Gisou van der Goot
and Demetrius Tsernoglou
Primary Structures .............................................................................. 79
The 3-D Structure .............................................................................. 81
Aero lysin Is a Dimer ........................................................................... 82
Mobility .............................................................................................. 84
Inhibition by Zinc Ions ....................................................................... 84
Receptor Binding ................................................................................ 85
Activation ........................................................................................... 85
Oligomerization .................................................................................. 87
Channel Formation ............................................................................. 88
Mechanism of Toxic Action ................................................................ 89
Relationship to Other Toxins .............................................................. 89
Conclusions and Future Studies .......................................................... 90
6. The Anthrax Toxin ................................................................... 97
Carlo Petosa and Robert C. Liddington
Intoxication by Anthrax ...................................................................... 98
Components of the Anthrax Toxin ................................................... 101
The PA Oligomer ........................................................................... 111
63
Homology With Iota-IB Toxin ......................................................... 111
A Hypothetical Model for Oligomerization
and Membrane Insertion ............................................................... 112
Concluding Remarks ........................................................................ 116
7. The Cholera Family ofEnterotoxins ....................................... 123
David L. Scott, Rong-Guang Zhang and Edwin M Westbrook
B Subunit Architecture ..................................................................... 124
The A (Catalytic) Subunit-Overview .............................................. 133
Mechanism of Action ........................................................................ 138
8. E. coli Heat Labile Enterotoxin and Cholera Toxin
B-Pentamer-Crystallographic Studies
of Biological Activity ............................................................... 147
Ethan A. Merritt, Focco van den Akker and Wim G.] Hoi
Architecture of the AB5 Assembly ..................................................... 150
Receptor Binding Site ....................................................................... 155
TheActiveSiteofLT ........................................................................ 158
Therapeutic Applications .................................................................. 163
9. Shiga Toxin ............................................................................ 173
Marie E. Fraser, Maia M. Chernaia, Yuri V. Kozlov
and Michael N. G. james
Description of the Holotoxin ............................................................ 174
B Pentamer ....................................................................................... 177
The Pore and A2 ............................................................................... 180
Other A-B Interactions ..................................................................... 183
The A Subunit .................................................................................. 184
Future Research ................................................................................ 186
10. Structural Insights into Pertussis Toxin Action ...................... 191
Penelope E. Stein, Bart Hazes and Randy J Read
Structure ofPertussis Toxin .............................................................. 194
Receptor Binding .............................................................................. 199
Intracellular Trafficking .................................................................... 202
ATP-Binding to Pertussis Toxin ....................................................... 203
Future Directions .............................................................................. 209
11. Structure ofTo xic Shock Syndrome T oxin-1 .......................... 217
Douglas H Ohlendorf, David T. Mitchell, G. Sridhar Prasad,
R. Radhakrishnan, Cathleen A. Earhart and Patrick M Schlievert
Biological Relevance .......................................................................... 217
Structure ofTSST-1 ......................................................................... 219
Functionally Important Features ....................................................... 223
12. Structure of Staphylococcal Enterotoxins ................................ 231
S. Swaminathan, William Furey and Martin Sax
Structure of SEB ............................................................................... 233
Structure of SEC2 ............................................................................. 233
Modeling of SEA and SEE ................................................................ 235
Mutational Analysis on SEB and Structural Features ......................... 236
TCR Binding Site ............................................................................. 239
MHCII Binding Site inS. Enterotoxins ............................................ 241
Possible Biological Role of the a4 Face of SEB .................................. 243
Emetic Site ........................................................................................ 243
V~ Specificity .................................................................................... 243
Oligomer Binding Fold and the Binding
of Glycosphingolipids to SEB ........................................................ 247
Conclusion ........................................................................................ 247
13. The Structure of Ribosome Inactivating
Proteins from Plants ............................................................... 253
jon D. Robertus and Arthur F Monzingo
Biochemistry Background of RIPs ..................................................... 254
X-Ray Structure of RIPs .................................................................... 255
Ricin A Chain ................................................................................... 256
The Ricin B Chain ............................................................................ 265
14. The Structures and Evolution of Snake Toxins
of the Three-Finger Folding Type .......................................... 271
Dominique Housset and juan C Fontecilla-Camps
Structural Comparison ofThree-Finger Snake Toxins ...................... 272
The Evolution ofThree-Finger Snake Toxins ................................... 281
15. The Structure of a Virally Encoded Fungal Toxin
from Ustilago Maydis that Inhibits Fungal
and Mammalian Calcium Channels ........................................ 291
Fei Gu, Anis Khimani, Stan Rane, William H. Flurkey,
Robert F Bozarth and Thomas J Smith
KP4 Structure ................................................................................... 293
Mechanisms ofKP4 Action Suggested by Its Structure ..................... 296
Biochemical Studies on KP4 Mechanism of Action ........................... 297
Conclusions ...................................................................................... 298
EDITOR
rr============== ================il
Michael W. Parker, D.Phil.
The Ian Potter Foundation Protein Crystallography Laboratory
St. Vincent's Institute of Medical Research
Melbourne, Australia
Chapter 2, Chapter 5
t======== CONTRIBUTORS ==========I
Joseph E. Alouf J. Thomas Buckley
Institut Pasteur Department of Biochemistry
Unite des Toxines Microbiennes and Microbiology
Paris, France University of Victoria
Chapter I British Columbia, Canada
Chapter 5
Charles E. Bell
Molecular Biology Institute Maia M. Chernaia
and UCLA DOE Laboratory Medical Research Council of Canada
of Structural Biology and Molecular Group in Protein Structure
Medicine and Function
University of California at Los Department of Biochemistry
Angeles University of Alberta
Los Angeles, California, USA Edmonton, Alberta, Canada
Chapter 3 Chapter 9
Melanie J. Bennett R. John Collier
Department of Biochemistry Department of Microbiology
and Biophysics and Molecular Genetics
School of Medicine, University Harvard Medical School, Shipley
of Pennsylvania Institute of Medicine
Philadelphia, Pennsylvania, USA Boston, Massachusetts, USA
Chapter3 Chapter3
Robert F. Bozarth Cathleen A. Earhart
Department ofLife Sciences Department of Biochemistry
Indiana State University University of Minnesota Medical
Terre Haute, Indiana, USA School
Chapter I5 Minneapolis, Minnesota, USA
Chapter II
David Eisenberg Bart Hazes
Molecular Biology Institute Department of Medical Microbiology
and UCLA DOE Laboratory and Immunology
of Structural Biology and University of Alberta
Molecular Medicine Edmonton, Alberta, Canada
University of California at Los Chapter 10
Angeles
Los Angeles, California, USA WimG.J. Hol
Chapter3 Biomolecular Structure Center
Howard Hughes Medical Institute
William H. Flurkey University ofWashington School of
Department of Chemistry Medicine
Indiana State University Seattle, Washington, USA
Terre Haute, Indiana, USA Chapter 8
Chapter 15
Dominique Housset
Juan C. Fontecilla-Camps lnstitut de Biologie Structurale Jean
Institut de Biologie Structurale Jean Pierre Ebel, CEA-CNRS
Pierre Ebel, CEA-CNRS Grenoble, France
Grenoble, France Chapter 14
Chapter14
Michael N.G. James
Marie E. Fraser Medical Research Council of Canada
Medical Research Council of Canada Group in Protein Structure and
Group in Protein Structure Function
and Function Department of Biochemistry
Department of Biochemistry University of Alberta
University of Alberta Edmonton, Alberta, Canada
Edmonton, Alberta, Canada Chapter 9
Chapter 9
Anis Khimani
William Furey Department of Life Sciences
Biocrystallography Laboratory Indiana State University
VA Medical Center Terre Haute, Indiana, USA
Pittsburgh, Pennsylvania, USA Chapter 15
Chapter 12
FeiGu
Department ofBiological Sciences
Purdue University
West Lafayette, Indiana, USA
Chapter 15
