Biosynthesis, Modification, and Processing of Cellular and Viral Polyproteins

341 Pages·1980·34.408 MB·English

by  Gebhard Koch (Eds.)

Biosynthesis, Modification, and Processing
of Cellular and Viral Polyproteins
Edited by
GEBHARD KOCH
Physiologisch-Chemisches Institut
der Universität Hamburg
Abteilung Molekularbiologie
Hamburg, West Germany
DIETMAR RICHTER
Physiologisch-Chemisches Institut
der Universität Hamburg
Abteilung Zellbiochemie
Hamburg, West Germany
1980
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Library of Congress Cataloging in Publication Data
Biosynthesis, modification, and processing of cel-
lular and viral polyproteins.
Proceedings of an international conference held
in Hamburg-Blankenese, Ger., May 27-31-1980.
Includes index.
1. Protein biosynthesis—Congresses.
2. Protein metabolism—Congresses. 3. Viruses—
Congresses. 4. Cellular control mechanisms—
Congresses. I. Koch, Gebhard. II. Richter,
Dietmar. [DNLM: 1. Proteins—Biosynthesis-
Congresses. 2. Proteins—Metabolism—Congresses.
3. Viral proteins—Biosynthesis—Congresses
4. Viral proteins—Metabolism—Congresses. QU55
P6185 1980]
QP551.B49 574.19'245 80-23010
ISBN 0-12-417560-0
PRINTED IN THE UNITED STATES OF AMERICA
80 81 82 83 9 8 7 6 5 4 3 2 1
Contributors
Numbers in parentheses indicate the pages on which authors' contributions begin.
C. J. Adler (309), Department of Microbiology, School of Basic Health
Sciences, State University of New York at Stony Brook, Stony Brook,
New York
P. C. Andrews (67), Department of Biochemistry, Purdue University, West
Lafayette, Indiana; and Department of Pharmacology and Toxicol-
ogy, University of Rochester School of Medicine, Rochester, New
York
D. Baltimore (301), Center for Cancer Research, and Department of Biol-
ogy, Massachusetts Institute of Technology, Cambridge, Massachu-
setts
P. Beguin (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Un-
iversity Pierre et Marie Curie, Paris, France
S. Benjannet (87), Protein and Pituitary Hormone Laboratory, Clinical Re-
search Institute of Montreal, Montreal, Canada
J. Bilello (185), Physiologisch-Chemisches Institut der Universität Ham-
burg, Abteilung Molekularbiologie, Hamburg, West Germany
M. Boucher (111), Department of Biology, Massachusetts Institute of Tech-
nology, Cambridge, Massachusetts
H. Boussetta (15), Groupe de Neurobiochemie Cellulaire et Moleculaire,
University Pierre et Marie Curie, Paris, France
D. Brauer (289), Max-Planck-Institut für Molekulare Genetik, Berlin, West
Germany
R. D. Broadwell (151), Laboratory of Biological Structure, National Dental
Institute, National Institutes of Health, Bethesda, Maryland
M. Budarf (127), Department of Chemistry, University of Oregon, Eugene,
Oregon 97403
ix
x CONTRIBUTORS
W. N. Burnette (233), Fred Hutchinson Cancer Research Center, Seattle,
Washington
M. Camier (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Un-
iv er site Pierre et Marie Curie, Paris, France
C. A. Carter (163), Department of Microbiology, School of Basic Health
Sciences, State University of New York at Stony Brook, Stony Brook,
New York
I. M. Chaiken (29), Laboratory of Chemical Biology, NIAM Department,
National Institute of Health, Bethesda, Maryland
A. C. Y. Chang (321), Departments of Genetics and Medicine, Stanford
University School of Medicine, Stanford, California 94305
M. Chretien (87), Protein and Pituitary Hormone Laboratory, Clinical Re-
search Institute of Montreal, Montreal, Canada
M. Cochet (321), Departments of Genetics and Medicine, Stanford Univer-
sity School of Medicine, Stanford, California 94305
J. Coffin (233), Tufts University School of Medicine, Boston, Massachusetts
P. Cohen (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Un-
iversity Pierre et Marie Curie, Paris, France
S. N. Cohen (321), Departments of Genetics and Medicine, Stanford Uni-
versity School of Medicine, Stanford, California 94305
T. D. Copeland (219), Biological Carcinogenesis Program, Frederick Can-
cer Research Center, Frederick, Maryland
P. Crine (87), Protein and Pituitary Hormone Laboratory, Clinical Research
Institute of Montreal, Montreal, Canada
P. Desbois (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Un-
iversity Pierre et Marie Curie, Paris, France
H. Diggelmann (233), Swiss Institute for Experimental Cancer Research,
Epalinges sur Lausanne, Switzerland
K. E. J. Dittmar (289), Max-Planck-Institut für Molekulare Genetik, Berlin,
West Germany
J. E. Dixon (67), Department of Biochemistry, Purdue University, West La-
fayette, Indiana; and Department of Pharmacology and Toxicology,
University of Rochester School of Medicine, Rochester, New York
R. Eisenman (233), Fred Hutchinson Cancer Research Center, Seattle,
Washington
C. Fahy (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Univer-
site Pierre et Marie Curie, Paris, France
W. Garten (175), Institut für Virologie der Justus-Liebig-Universität, Geis-
sen, West Germany
C. Gianoulakis (87), Protein and Pituitary Hormone Laboratory, Clinical
Research Institute of Montreal, Montreal, Canada
C. Glembotski (139), Department of Physiology, C-240, University of Colo-
rado, Denver, Colorado
F. Gossard (87), Protein and Pituitary Hormone Laboratory, Clinical Re-
search Institute of Montreal, Montreal, Canada
CONTRIBUTORS XI
P. A. Hargrave (29), Laboratory of Chemical Biology, NIAM Department,
National Institutes of Health, Bethesda, Maryland
P. Heater (233), Fred Hutchinson Cancer Research Center, Seattle, Wash-
ington
L. E. Henderson (219), Biological Carcinogenesis Program, Frederick Can-
cer Research Center, Frederick, Maryland
E. Herbert (127), Department of Chemistry, University of Oregon, Eugene,
Oregon
E. Hiller (249), Physiologisch-Chemisches Institut der Universität Ham-
burg, Abteilung Molekularbiologie, Hamburg, West Germany
P. M. Hinkle (67), Department of Biochemistry, Purdue University, West
Lafayette, Indiana; and Department of Pharmacology and Toxicol-
ogy, University of Rochester School of Medicine, Rochester, New
York
C. J. Hough (29), Laboratory of Chemical Biology, NIAM Department, Na-
tional Institutes of Health, Bethesda, Maryland
R. I veil (5,43), Physiologisch-Chemisches Institut der Universität
Hamburg, Abteilung Zellbiochemie, Hamburg, West Germany
B. G. Jenks (151), Laboratory of Developmental Neurobiology, National
Institute of Child Health and Human Development, Bethesda, Mary-
land
B. N. Jones (99), Roche Institute of Molecular Biology, Nutley, New Jersey
W. Keil (175), Institut für Virologie der Justus-Liebig-Universität, Geissen,
West Germany
D. L. Kilpatrick (99), Roche Institute of Molecular Biology, Nutley, New
Jersey
S. Kimura (99), Roche Institute of Molecular Biology, Nutley, New Jersey
N. Kitamura (309), Department of Microbiology, School of Basic Health
Sciences, State University of New York at Stony Brook, Stony Brook,
New York
H.-D. Klenk (175), Institut für Virologie der Justus-Liebig-Universität, des-
sen, West Germany
G. Koch (185, 249), Physiologisch-Chemisches Institut der Universität
Hamburg, Abteilung Molekularbiologie, Hamburg, West Germany
K. Kojima (99), Roche Institute of Molecular Biology, Nutley, New Jer-
sey
B. D. Korant (277), Central Research and Development Department,
Du Pont Experimental Station, Wilmington, Delaware
J. Langner (277), Physiologisch-Chemisches Institut, Martin-Luther-Un-
iversität, Halle (Saale), Federal Republic of Germany
N. Lariviere (87), Protein and Pituitary Hormone Laboratory, Clinical Re-
search Institute of Montreal, Montreal, Canada
M. Lauber (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Un-
iversite Pierre et Marie Curie, Paris, France
R. V. Lewis (99), Roche Institute of Molecular Biology, Nutley, New Jersey
CONTRIBUTORS
Xll
B. Y. Lin (163), Department of Microbiology, School of Basic Health Sci-
ences, State University of New York at Stony Brook, Stony Brook,
New York
H. F. Lodish (111, 329), Department of Biology, Massachusetts Institute of
Technology, Cambridge, Massachusetts
Y. P. Loh (151), Laboratory of Developmental Neurobiology, National In-
stitute of Child Health and Human Development, Bethesda, Maryland
R. B. Luftig (203), Department of Microbiology and Immunology, Univer-
sity of South Carolina, School of Medicine, Columbia, South Carolina
M. J. O. Masse (15), Groupe de Neurobiochimie Cellulaire et Moleculaire,
Universite Pierre et Marie Curie, Paris, France, C. D.
C. D. Minth (67), Department of Biochemistry, Purdue University, West La-
fayette, Indiana; and Department of Pharmacology and Toxicology,
University of Rochester School of Medicine, Rochester, New York
K. Moelling (289), Max-Planck-Institut für Molekulare Genetik, Berlin,
West Germany
P. Nicolas (15), Groupe de Neurobiochemie Cellulaire et Moleculaire, Un-
iversite Pierre et Marie Curie, Paris, France
H. Niemann (175), Institut für Virologie der Justus-Liebig-Universität, Geis-
sen, West Germany
S. Oroszlan (219), Biological Carcinogenesis Program, Frederick Cancer
Research Center, Frederick, Maryland
M. A. Pallansch (263), Biophysics Laboratory, University of Wisconsin,
Madison, Wisconsin
A. C. Palmenberg (263), Biophysics Laboratory, University of Wisconsin,
Madison, Wisconsin
P. Policastro (127), Department of Chemistry, University of Oregon,
Eugene, Oregon 97403
M. Porter (111), Department of Biology, Massachusetts Institute of Tech-
nology, Cambridge, Massachusetts
J. C. Powers (277), School of Chemistry, Georgia Institute of Technology,
Atlanta, Georgia
R. O. Pozzatti (163), Department of Microbiology, School of Basic Health
Sciences, State University of New York at Stony Brook, Stony Brook,
New York
E. M. Rabin (219), Biological Carcinogenesis Program, Frederick Cancer
Research Center, Frederick, Maryland
D. Richter (5, 43), Physiologisch-Chemisches Institut der Universität Ham-
burg, Abteilung Zellbiochemie, Hamburg, West Germany
P. A. Rosa (127), Department of Chemistry, University of Oregon, Eugene,
Oregon 97403
P. G. Rothberg (309), Department of Microbiology, School of Basic Health
Sciences, State University of New York at Stony Brook, Stony Brook,
New York
R. Rott (175), Institut für Virologie der Justus-Liebig-Universität, Geissen,
West Germany
CONTRIBUTORS XIII
R. R. Rueckert (263), Biophysics Laboratory, University of Wisconsin,
Madison, Wisconsin
J. H. Rupnow (67), Department of Biochemistry, Purdue University, West
Lafayette, Indiana; and Department of Pharmacology and Toxicol-
ogy, University of Rochester School of Medicine, Rochester, New
York
C. Schärli (249), Physiologisch-Chemisches Institut der Universität Ham-
burg, Abteilung Molekularbiologie, Hamburg, West Germany
H. Schmale (5, 43), Physiologisch-Chemisches Institut der Universität
Hamburg, Abteilung Zellbiochemie, Hamburg, West Germany
C. Schmidt (43), Physiologisch-Chemisches Institut der Universität Ham-
burg, Abteilung Zellbiochemie, Hamburg, West Germany
A. M. Schultz (219), Biological Carcinogenesis Program, Frederick Cancer
Research Center, Frederick, Maryland
R. T. Schwarz (175), Institut für Virologie der Justus-Liebig-Universität,
Geissen, West Germany
M. Schweiger (1), Institute for Biochemistry, University of Innsbruck, Inns-
bruck, Austria
N. G. Seidah (87), Protein and Pituitary Hormone Laboratory, Clinical Re-
search Institute of Montreal, Montreal, Canada
J. E. Shively (99), City of Hope National Medical Center, Duarte, Califor-
nia
J. Spiess (79), Peptide Biology Laboratory, The Salk Institute, San Diego,
California 92138
S. Stein (99), Roche Institute of Molecular Biology, Nutley, New Jersey
A. S. Stern (99), Roche Institute of Molecular Biology, Nutley, New Jer-
sey
G. J. A. M. Strous (111), Department of Biology, Massachusetts Institute of
Technology, Cambridge, Massachusetts
W. L. Taylor (67), Department of Biochemistry, Purdue University, West
Lafayette, Indiana; and Department of Pharmacology and Toxicol-
ogy, University of Rochester School of Medicine, Rochester, New
York
P. Traktman (301), Center for Cancer Research and Department of Biol-
ogy, Massachusetts Institute of Technology, Cambridge, Massachu-
setts
P. Tsichlis (233), Tufts University School of Medicine, Boston, Massachu-
setts
S. Udenfriend (99), Roche Institute of Molecular Biology, Nutley, New Jer-
sey
W. Vale (79), Peptide Biology Laboratory, The Salk Institute, San Diego,
California 92138
J. Villarreal (79), Peptide Biology Laboratory, The Salk Institute, San
Diego, California 92138
G. Warnecke (185), Physiologisch-Chemisches Institut der Universität
Hamburg, Abteilung Molekularbiologie, Hamburg, West Germany
XIV CONTRIBUTORS
C. Weber (185), Physiologisch-Chemisches Institut der Universität Ham-
burg, Abteilung Molekularbiologie, Hamburg, West Germany
E. Wimmer (309), Department of Microbiology, School of Basic Health Sci-
ences, State University of New York at Stony Brook, Stony Brook,
New York
Y. Yoshinaka (203), Department of Microbiology and Immunology, Univer-
sity of South Carolina, School of Medicine, Columbia, South Carolina
A. Zilberstein (111), Department of Biology, Massachusetts Institute of
Technology, Cambridge, Massachusetts
F. Zucco (233), Swiss Institute for Experimental Cancer Research, Epa-
linges sur Lausanne, Switzerland
Foreword
When the process of protein synthesis was first described, it seemed rea-
sonable to expect that if the cell had gone to all that trouble to make a protein
it would not then start chewing it up. But, year by year, new examples of
how recently made proteins are processed by proteolysis have emerged. The
activation of intestinal proteases and circulating hormones were early exam-
ples but, especially as a consequence of the study of viruses, many examples
of intracellular processing have been uncovered. Because so many proteins
lose their N-terminal methionine, secondary proteolysis following synthesis
of proteins has turned out to be the rule rather than the exception.
The example of poliovirus is especially instructive because proteolysis
plays such a large role in the synthesis of poliovirus protein. A single precur-
sor polypeptide gives rise to all of the known poliovirus proteins in a cascade
of proteolytic events. The first level of proteolysis is the cleavage of the
nascent polypeptide chain, a process apparently carried out by cellular en-
zymes. Why such cellular enzymes exist and what kinds of signals they read
on the viral protein are important questions for the future. Because the nas-
cent polypeptide cleavages occur so rapidly after the synthesis of a sensitive
bond, it is also important to ask whether the proteases are ribosome-bound
or free in the cytoplasm. A similar type of proteolysis occurs with togavirus
proteins, and there the question of membrane involvement is important be-
cause some of the proteins are surface glycoproteins of the virus. The possi-
ble involvement of membranes in poliovirus protein synthesis has been sug-
gested for many years, but no role for membrane attachment nor any
understanding of how the membrane attachment might occur has yet devel-
oped.
After the initial nascent cleavages, the poliovirus proteins undergo a series
of slower, cytoplasmic cleavages. Some of these are carried out by viral
enzymes, but some may be carried out by cellular enzymes and the exact
XV
XVI FOREWORD
relationship between the proteases and the proteins is still a matter of some
debate. In one case, the final maturational cleavage of the virion, the pro-
teolytic event seems to be coupled to the attainment of a specific particle
morphology. Whether there is coupling of the other proteolytic events to
biochemical processes is not clear.
A final important question is why poliovirus and many other viruses have
chosen to make long precursor proteins and have them cleaved by proteases
rather than having individual messages for the individual proteins. It is clear
from the study of other RNA viruses that strategies that allow the synthesis
of individual messenger RNAs are easily available to viruses. We suggested
many years ago that if a virus is to use only a single messenger RNA it may
be forced to make a polyprotein because mammalian messenger RNAs
might only be able to initiate a single protein on a single messenger RNA.
This suggestion has held up well: No example of the initiation of multiple
polypeptides from a single messenger RNA has yet been reported. There
are, however, many examples showing that the first AUG on a messenger
RNA is not the one that is used for protein synthesis. An important question
for the future is why the first AUG on a messenger RNA is not the one that is
used for protein synthesis. Another important question for the future is
whether the first AUG can function at all. Until the details of the mechanism
by which ribosomes recognize and read messenger RNAs have been worked
out, we shall probably not know the underlying reason for polioviruses hav-
ing evolved such an apparently cumbersome mechanism to make their pro-
teins.
The previous discussion underlines the importance of understanding the
details of viral protein synthesis. The mechanisms used by viruses tell us an
enormous amount about cell protein synthesis, and the viruses provide
models for understanding the cell. The extensive proteolytic processing un-
dergone by viral proteins does not yet have explicit counterparts among cel-
lular proteins because most cellular proteins are made from individual mes-
senger RNAs rather than as part of large polyproteins. But it must be that
some fraction of cellular proteins are processed by cellular proteases be-
cause it is hard to believe that the nascent proteolytic cleavage systems have
evolved to help viruses infect cells. Such proteases may play a role in the
synthesis of neural peptides. It should be interesting to observe in future
years the new roles in cellular metabolism uncovered for the enzymes that
aid viral development.
David Baltimore
Center for Cancer Research
and Department of Biology
Massachusetts Institute of Technology
Cambridge, Massachusetts