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  • Viral Membrane Proteins: Structure, Function, and Drug Design

  • PROTEIN REVIEWS

    Editorial Board:

    EDITOR-IN-CHIEF: M. ZOUHAIR ATASSI, Baylor College of Medicine, Houston, Texas

    EDITORIAL BOARD: LAWRENCE J. BERLINER, University of Denver, Denver, Colorado ROWEN JUI-YOA CHANG, University of Texas, Houston, Texas HANS JÖRNVALL, Karolinska Institutet, Stockholm, Sweden GEORGE L. KENYON, University of Michigan, Ann Arbor, Michigan BRIGITTE WITTMAN-LIEBOLD, Wittman Institute of Technology and Analysis, Tetlow, Germany

    Recent Volumes in this Series

    VIRAL MEMBRANE PROTEINS: STRUCTURE, FUNCTION, AND DRUG DESIGN Edited by Wolfgang B. Fischer

    A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information, please contact the publisher.

  • Viral Membrane Proteins: Structure, Function, and Drug Design

    Edited by

    WOLFGANG B. FISCHER Department of Biochemistry, University of Oxford, United Kingdom

    Kluwer Academic / Plenum Publishers New York, Boston, Dordrecht, London, Moscow

  • ISBN 0-306-48495-1 Hardback

    © 2005 by Kluwer Academic/Plenum Publishers, New York 233 Spring Street, New York, N.Y. 10013

    http://www.kluweronline.com

    10 9 8 7 6 5 4 3 2 1

    A C.I.P. record for this book is available from the Library of Congress.

    All rights reserved

    No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.

    Permissions for books published in Europe: permissions@wkap.nl Permissions for books published in the United States of America: permissions@wkap.com

    Printed in the United States of America

    Library of Congress Cataloging-in-Publication Data

    Viral membrane proteins: structure, function, and drug design / edited by Wolfgang Fischer.

    p. cm. – (Protein reviews) Includes bibliographical references and index. ISBN 0-306-48495-1 1. Viral proteins. I. Fischer, Wolfgang (Wolfgang B.) II. Series.

    QR460.V55 2005 616.9�101–dc22

    2004042175

  • Contents

    List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

    Part I. Membrane Proteins from Plant Viruses

    1. Membrane Proteins in Plant Viruses

    Michael J. Adams and John F. Antoniw

    1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. Survey of Transmembrane Proteins in Plant Viruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

    2.1. The Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.2. Software . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

    3. Cell-to-Cell Movement Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3.1. The “30K” Superfamily . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.2. Triple Gene Block . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 3.3. Carmovirus-Like . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3.4. Other Movement Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.5. General Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

    4. Replication Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 5. Proteins Involved in Transmission by Vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

    5.1. Insect Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 5.1.1. Persistent Transmission by Aphids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 5.1.2. Transmission by Hoppers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 5.1.3. Transmission by Thrips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 5.1.4. Persistent Transmission by Whiteflies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

    5.2. Fungus Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 6. Other Membrane Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

    2. Structure and Function of a Viral Encoded K� Channel

    Anna Moroni, James Van Etten, and Gerhard Thiel

    1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 2. K� Channels are Highly Conserved Proteins with Important Physiological Functions . . . . 22 3. Structural Aspects of Viral K� Channel Proteins as Compared to those

    from Other Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 4. The Short N-Terminus is Important for Kcv Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

    v

  • 5. Functional Properties of Kcv Conductance in Heterologous Expression Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

    6. Kcv is a K� Selective Channel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 7. Kcv has Some Voltage Dependency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 8. Kcv has Distinct Sensitivity to K� Channel Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 9. Ion Channel Function in Viral Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

    10. Kcv is Important for Viral Replication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 11. Evolutionary Aspects of the kcv Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

    Part II. Fusion Proteins

    3. HIV gp41: A Viral Membrane Fusion Machine

    Sergio G. Peisajovich and Yechiel Shai

    1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 2. HIV Envelope Native Conformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 3. Receptor-Induced Conformational Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

    3.1. CD4 Interaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 3.2. Co-Receptor Interaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

    4. The Actual Membrane Fusion Step . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.1. The Role of the N-Terminal Fusion Domain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.2. The Role of the C-Terminal Fusion Domain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

    5. HIV Entry Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 5.1. CD4-Binding Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 5.2. Co-Receptor-Binding Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 5.3. Improving the Activity of Inhibitors that Block Conformational Changes . . . . . . . . . . . 42

    6. Final Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

    4. Diversity of Corona

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