Horizons in Biochemistry and Biophysics Series somes, glyoxysomes, and lysosomes. The two mitochondrial

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  • Horizons in Biochemistry and Biophysics


    Editorial Board

    J . J . Blum D e p a r t m e n t of P h y s i o l o g y a n d P h a r m a c o l o g y y D u k e U n i v e r s i t y M e d i c a l C e n t r e , D u r h a m , N o r t h C a r o l i n a , U.S.A.

    L . Ernster D e p a r t m e n t of B i o c h e m i s t r y , A r r h e n i u s L a b o r a t o r y , U n i v e r s i t y of S t o c k h o l m , S t o c k h o l m , Sweden

    H. R. Kaback Roche I n s t i t u t e of M o l e c u l a r B i o l o g y , N u t l e y , New Jersey, U.S.A.

    J. Knoll D e p a r t m e n t of P h a r m a c o l o g y , Semmelweis U n i v e r s i t y of M e d i a n e , Budapest, H u n g a r y K.D. Kohn L a b o r a t o r y of B i o c h e m i c a l P h a r m a c o l o g y , N a t i o n a l I n s t i t u t e of A r t h r i t i s , M e t a b o l i s m a n d D i g e s t i v e Diseases, N a t i o n a l I n s t i t u t e s of H e a l t h , Bethesda, M a r y l a n d , U.S.A.

    H. L . Kornberg, F.R.S. D e p a r t m e n t of B i o c h e m i s t r y , U n i v e r s i t y of C a m b r i d g e , E n g l a n d

    A. M . Kroon L a b o r a t o r y of P h y s i o l o g i c a l C h e m i s t r y , U n i v e r s i t y of G r o n i n g e n , G r o n i n g e n , The N e t h e r l a n d s

    F. Palmieri, M a n a g i n g E d i t o r D e p a r t m e n t of P h a r m a c o - B i o l o g y , L a b o r a t o r y of B i o c h e m i s t r y , U n i v e r s i t y of B a r i , I t a l y

    E. Quagliariello, E d i t o r - i n - C h i e f D e p a r t m e n t of B i o c h e m i s t r y , U n i v e r s i t y of B a r i , I t a l y

  • Horizons in Biochemistry and Biophysics

    S t r u c t u r e a n d E x p r e s s i o n V o l u m e E d i t o r A. M . Kroon

    Laboratory of Physiological Chemistry, University of G r o n i n g e n ,

    G r o n i n g e n , T h e Netherlands

    Series E d i t o r s E. Quagliariello

    Department of Biochemistry, University of B a r i

    F. Palmieri Department of Pharmaco-Biology,

    Laboratory of Biochemistry, University of B a r i

    A Wiley-lnterscience P u b l i c a t i o n

    V o l u m e 7


    JOHN W I L E Y & SONS C h i c h e s t e r • New Y o r k • B r i s b a n e • T o r o n t o • S i n g a p o r e

  • Contents

    List of Contributors vii

    Preface ix 1 The structure of nucleosomes and chromatin 1

    A . K L U G A N D P . J . G . B U T L E R

    2 Activation and function of chromatin 4 3 P . N . B R Y A N A N D O . H . J . D E S T R E E

    3 Structure and function of ribosomal RNA 91 H . F . N O L L E R A N D P . H . V A N K N I P P E N B E R G

    4 Structure and role of eubacterial ribosomal proteins 101 R . A . G A R R E T T

    5 Regulatory steps in the initiation of protein synthesis 1 3 9 H . O . V O O R M A

    6 Transport of proteins from the sites of genetic expression to their sites of functional expression: protein conformation and thermodynamic aspects 155 C. K E M P F , R . D . K L A U S N E R , R . B L U M E N T H A L A N D J . V A N R E N S W O U D E

    7 Approaches to the study of hormonal regulation of gene expression 171 A . J . W Y N S H A W - B O R I S A N D R . W . H A N S O N

    8 Strategies for optimizing foreign gene expression in Escherichia coli 2 0 5 H . A . D E B O E R A N D H . M . S H E P A R D

    9 Interplay between different genetic Systems in eukaryotic cells: nucleocytoplasmic-mitochondrial interrelations 2 4 9 H . DE V R I E S A N D P . V A N T S A N T

    10 Mosaic genes and RNA processing in mitochondria 2 7 9 L . A . G R I V E L L , L . B Ö N E N A N D P . B O R S T

    11 Assembly of mitochondrial proteins 3 0 7 B . H E N N I G A N D W . N E U P E R T

    12 The non-universality of the genetic code 3 4 7 A . M . K R O O N A N D S . S A C C O N E

    Index 3 5 7

  • Genes: Structure and Expression Edited by A . M . Kroon © 1983 John Wiley & Sons Ltd.


    Bernd Hennig and Walter Neupert


    The eucaryotic c e l l i s organized by a variety of membranes: the

    plasma membrane which forms the border of the c e l l and various

    intracellular membranes which delimit the various organelles. In

    most c e l l s intracellular membranes greatly exceed the plasma mem-

    brane with respect to surface area. The diverse membranes of the

    c e l l have properties in common which are the basis for compartmenta-

    tion: a) membranes possess identity, i.e. with few exceptions each

    particular membrane of a c e l l has a unique protein composition;

    b) membranes have continuity r not only in space but also in time,

    i.e. membranes are formed by insertion of newly made components into

    preexistent membranes; c) membranes display selective permeability,

    i.e. they prevent the free diffusion of most molecules between the

    two separated Spaces.

    A membrane gives the compartment which i t encloses identity:

    It determines the protein composition of the luminal or cisternal

    space ("matrix") of that organeile. This is because the proteins of

    the various organelles and their membranes - with only very few

    exceptions - are not synthesized in the same compartments where

    their functional sites are located. Rather, they are synthesized on

    cytoplasmic ribosomes and have to be selectively translocated across

    the diverse membranes. Organelle membranes therefore must not only

    have devices to specif i c a l l y recognize proteins which are destined


  • 308

    for the compartment they enclose, but also have mechanisras to

    translocate these proteins across the l i p i d bilayer. This is quite

    remarkable in light of the fact that many of these proteins are not

    only large but also very hydrophilic. Therefore, translocation of

    newly formed proteins across membranes and their intracellular

    sorting are quite puzzling phenomena.


    According to our present knowledge, two different mechanisms

    are involved in the translocation of proteins across membranes and

    their insertion into membranes (1). Cotranslational mechanisms are

    employed with proteins which traverse the membrane of the endoplas-

    mic reticulum (ER). In contrast, the import of proteins into orga-

    nelles such as mitochondria, chloroplasts, and probably peroxisomes

    and glyoxysomes is apparently the result of posttranslational pro-

    cesses. Some proteins of the ER and the plasma membrane appear to

    u t i l i z e this latter mode of transport as well.

    Cotranslational Transport: The Translocation of Proteins Is Coupled

    to the Elongation of the Nascent Polypeptides.

    Many proteins are translated on polysomes tightly associated

    with the ER. They are cotranslationally inserted into or transferred

    across the membraner i.e. this process is concomitant with Polypep-

    tide chain elongation. Glycosylation of nascent Polypeptide chains

    has been observed, and i t i s generally accepted that glycosylation

    occurs only in the luminal space of the ER (2). Completed Polypep-

    tides are never seen on the cytosolic side of the membrane which

    binds the ribosomes. Cotranslationally transported proteins can be

    synthesized in vitro in cell-free translation Systems as complete

    precursors but they never cross the membrane of vesicles derived

  • 309

    from the ER unless those vesicles are present during translation.

    A detailed mechanism by which cotranslationally transported

    proteins reach their proper positions was f i r s t proposed in the

    "signal hypothesis" and has been extensively modified in response to

    new data (3). A large body of evidence now supports a mechanism

    which entails the following Steps: Synthesis of the Polypeptide

    begins on free ribosomes. The nascent Polypeptide carries an amino-

    terminal presequence of 15 - 30 amino acid residues representing the

    "signal sequence". The signal sequence protrudes out of the ribosome

    when a Polypeptide of about 60 - 70 amino acid residues in length

    has been synthesized. An oligomeric "signal recognition protein"

    (SRP) binds to the freely accessible signal sequence and arrests

    further elongation of the Polypeptide. The SRP - polysome complex

    then interacts with an SRP receptor or "docking protein" at the ER

    membrane (4). This releases the arrest of elongation and results in

    the nascent Polypeptide chain penetrating the membrane.

    Recognition in this cotranslational transfer thus seems to

    involve two specific interactions: the signal sequence interacts

    with the SRP, and the SRP interacts with i t s receptor on the mem-

    brane. Further proteins such as the "ribophorins" may stabilize the

    ribosome - membrane interaction (5). The signal sequence is cleaved

    off the Polypeptide before peptide elongation is completed. This is

    accomplished by the "signal peptidase", an integral membrane protein

    which i s probably located at the luminal side of the ER membrane

    (6). According to Information inherent in the structure of the Poly-

    peptide chain, the protein w i l l be transferred either