membrane surrounding most compartments of eukaryotic cells, or folded into a β-barrel, as is
the case for all MPs of bacterial outer membranes and a few MPs from the outer membranes
of mitochondria and chloroplasts.
• Finally, many protein subunits are simply associated non-covalently to MPs themselves
without being in direct contact with the lipids (Fig. 1.5A, Scheme ⑤). These proteins are
called “extrinsic” MPs, because they can be removed by treatments, like extremes of pH or
ionic strength, that do not disrupt the membrane itself.
Those MPs whose polypeptide chain is in direct contact with the hydrophobic core of the
membrane (Fig. 1.5A, Schemes ③, ④, ⑥, ⑦) are called “integral” or “intrinsic” (Singer and Nicolson
1972). They cannot, with few exceptions, be extracted without resorting to strong surfactants, which
will break the membrane apart (see Chap. 2). A nomenclature introduced by Günter Blobel (Blobel
1980) distinguishes those integral MPs that penetrate the lipid core but do not span it, called monotopic
integral MPs (because they contact only one aqueous phase; Fig. 1.5A, Scheme ③), from those that
span it once, and thus comprise one region in contact with each of the two aqueous phases separated by
the membrane (called bitopic MPs; Schemes ④, ⑥; an admittedly somewhat confusing term given
that these MPs sport a single TM segment, not two) and those that span it two or more times (called
polytopic MPs; Scheme ⑦). Integral MPs can be further anchored to the membrane by covalently
attached lipids (Scheme ⑥). Many MPs are organized into homo- or hetero-oligomers, which can
comprise several subunits (sometimes tens of them), often associating bitopic and polytopic MPs
to extrinsic ones (see e.g. Figs. 1.13 and 1.21). The complexes can themselves associate into
supercomplexes, such as the mitochondrial “respirasome,” which associates one copy of Complex I
(the NADH:ubiquinone oxidoreductase), a dimer of Complex III (cytochrome bc 1 ), and one copy of
Complex IV (cytochrome c oxidase) (see Chap. 12, Fig. 12.17).
1.4.2
Structure of Transmembrane Protein Regions
In this book, we will be mostly concerned with bitopic and polytopic MPs. There are two major reasons
for this focus:
(i) Very few data are currently available about applying APols and other nonconventional
surfactants to studying monotopic integral MPs.
(ii) A major advantage of APols is their mildness toward lipid-embedded protein domains,
which do not exist in anchored proteins; APols can certainly be useful, in specific cases, for
handling anchored proteins in vitro (e.g. when the protein is vulnerable to detergents and the
anchor cannot be deleted, or to attach these proteins onto solid supports via functionalized
APols, to deliver them to membranes, etc.), but to date such experiments have been
described only for TM proteins.
The following discussion focuses on TM protein regions, because it is those with which APols
and other surfactants have been designed to interact. APols can also interact with extramembrane
regions, a point that will be discussed in Chap. 5. The organization of these regions, however, raises
few specific issues as compared to soluble proteins.
It is beyond the scope of the present book to present an exhaustive overview of MP structures,
and only some general guidelines will be proposed, particularly where they are essential to understanding the mode of action of APols and other nonconventional surfactants, the reason(s) of their
mildness toward MPs as compared to detergents, and as a help to solving problems that their use can
1.4 Membrane Protein Structure
15
the case for all MPs of bacterial outer membranes and a few MPs from the outer membranes
of mitochondria and chloroplasts.
• Finally, many protein subunits are simply associated non-covalently to MPs themselves
without being in direct contact with the lipids (Fig. 1.5A, Scheme ⑤). These proteins are
called “extrinsic” MPs, because they can be removed by treatments, like extremes of pH or
ionic strength, that do not disrupt the membrane itself.
Those MPs whose polypeptide chain is in direct contact with the hydrophobic core of the
membrane (Fig. 1.5A, Schemes ③, ④, ⑥, ⑦) are called “integral” or “intrinsic” (Singer and Nicolson
1972). They cannot, with few exceptions, be extracted without resorting to strong surfactants, which
will break the membrane apart (see Chap. 2). A nomenclature introduced by Günter Blobel (Blobel
1980) distinguishes those integral MPs that penetrate the lipid core but do not span it, called monotopic
integral MPs (because they contact only one aqueous phase; Fig. 1.5A, Scheme ③), from those that
span it once, and thus comprise one region in contact with each of the two aqueous phases separated by
the membrane (called bitopic MPs; Schemes ④, ⑥; an admittedly somewhat confusing term given
that these MPs sport a single TM segment, not two) and those that span it two or more times (called
polytopic MPs; Scheme ⑦). Integral MPs can be further anchored to the membrane by covalently
attached lipids (Scheme ⑥). Many MPs are organized into homo- or hetero-oligomers, which can
comprise several subunits (sometimes tens of them), often associating bitopic and polytopic MPs
to extrinsic ones (see e.g. Figs. 1.13 and 1.21). The complexes can themselves associate into
supercomplexes, such as the mitochondrial “respirasome,” which associates one copy of Complex I
(the NADH:ubiquinone oxidoreductase), a dimer of Complex III (cytochrome bc 1 ), and one copy of
Complex IV (cytochrome c oxidase) (see Chap. 12, Fig. 12.17).
1.4.2
Structure of Transmembrane Protein Regions
In this book, we will be mostly concerned with bitopic and polytopic MPs. There are two major reasons
for this focus:
(i) Very few data are currently available about applying APols and other nonconventional
surfactants to studying monotopic integral MPs.
(ii) A major advantage of APols is their mildness toward lipid-embedded protein domains,
which do not exist in anchored proteins; APols can certainly be useful, in specific cases, for
handling anchored proteins in vitro (e.g. when the protein is vulnerable to detergents and the
anchor cannot be deleted, or to attach these proteins onto solid supports via functionalized
APols, to deliver them to membranes, etc.), but to date such experiments have been
described only for TM proteins.
The following discussion focuses on TM protein regions, because it is those with which APols
and other surfactants have been designed to interact. APols can also interact with extramembrane
regions, a point that will be discussed in Chap. 5. The organization of these regions, however, raises
few specific issues as compared to soluble proteins.
It is beyond the scope of the present book to present an exhaustive overview of MP structures,
and only some general guidelines will be proposed, particularly where they are essential to understanding the mode of action of APols and other nonconventional surfactants, the reason(s) of their
mildness toward MPs as compared to detergents, and as a help to solving problems that their use can
1.4 Membrane Protein Structure
15