exciting the postsynaptic cell. Budding, migration, and fusion result in the transport of solutes
and membrane components from one cell compartment to another. During their biosynthesis,
MPs are first integrated into the endoplasmic reticulum (ER) membrane (see § 1.7.1). Those
MPs that have been correctly modified posttranslationally and, if applicable, oligomerized
accumulate into vesicles that bud from the ER and fuse with the cis cisternae of the Golgi
apparatus, after which, by a succession of fission and fusion events, they move from one
compartment of the Golgi to another and, finally, reach the plasma membrane. Some MPs
from the plasma membrane are internalized when they have bound a hormone or a nutrient.
Thus, the low-density lipoprotein (LDL) receptors, once loaded with the cargo they have
picked from the blood, are internalized into endocytic vesicles that fuse with cytosolic
compartments called endosomes, the internal pH of which is low (from pH 6.0–6.5 in early
endosomes to pH 4.5–5.5 in late endosomes and lysosomes). This pH drop is the signal for
LDL and its receptor to dissociate one from another. The receptor migrates back to the cell
surface, whereas the LDL is transported to lysosomes, where it will be degraded and its
components metabolized. This mechanism is exploited by many viruses, such as that of flu:
hemagglutinin, a MP of the viral envelope, binds to cell-surface oligosaccharides containing
sialic acids, upon which viral particles are transported to endosomes. At low pH, hemagglutinin undergoes a conformational change, exposing a hydrophobic segment that interacts with
the endosomal membrane and brings about its fusion with the viral envelope, releasing the
nucleic acid of the virus into the cytosol, where it will be transcripted and replicated. Newly
synthesized viral envelope MPs are integrated into the ER and transported to the plasma
membrane, where they bind the viral nucleic acid and its associated proteins. Viral particles
bud and are released in the extracellular medium, launching a new cycle.
• MPs are involved in transferring soluble proteins across the plasma membrane of bacteria,
across the two-membrane envelope of Gram
À bacteria, across the membrane and into the
lumen of the endoplasmic reticulum, into mitochondria and chloroplasts, etc., as well as in
integrating into one or the other target membrane newly synthesized MPs, either in the course
of their synthesis or posttranslationally (see § 1.7.1).
• Some membrane proteins are involved in structuring cells and tissues. “Band 3,” for instance,
the red blood cell anion exchanger, comprises, in addition to its TM domain, a cytosolic one
that interacts with the cytoskeleton, playing a critical role in determining the mechanical
properties of the cell. In the gap junctions, connexons integrated in the plasma membrane of
two neighboring cells not only dock one onto the other to form an aqueous channel that spans
the two plasma membranes, through which small molecules can diffuse from the cytosol of
one cell to that of the other: they also mechanically associate the two cells one with another.
This quick and somewhat shallow overview of the tasks that MPs fulfill is quite patchy, but it
gives an idea of what they must be able to achieve: form pores and regulate their specificity and their
opening; recognize, bind, and import solutes, some of them small (ions, small molecules), some very
large (proteins); transduce energy and information; associate mechanically membranes to each other or
to inside or outside structures; and carry out the budding, transport and fusion of vesicles, etc. In the
next section, we shall examine which structures have evolved to achieve such tasks. Forming a clear
view of the kinds of structure adopted by MPs and what stabilizes them is indeed essential to
understanding the problems encountered when handling them in aqueous solutions, and why certain
types of surfactants are better than others at keeping those under control.
12
1 Membrane Proteins and Their Natural Environment
and membrane components from one cell compartment to another. During their biosynthesis,
MPs are first integrated into the endoplasmic reticulum (ER) membrane (see § 1.7.1). Those
MPs that have been correctly modified posttranslationally and, if applicable, oligomerized
accumulate into vesicles that bud from the ER and fuse with the cis cisternae of the Golgi
apparatus, after which, by a succession of fission and fusion events, they move from one
compartment of the Golgi to another and, finally, reach the plasma membrane. Some MPs
from the plasma membrane are internalized when they have bound a hormone or a nutrient.
Thus, the low-density lipoprotein (LDL) receptors, once loaded with the cargo they have
picked from the blood, are internalized into endocytic vesicles that fuse with cytosolic
compartments called endosomes, the internal pH of which is low (from pH 6.0–6.5 in early
endosomes to pH 4.5–5.5 in late endosomes and lysosomes). This pH drop is the signal for
LDL and its receptor to dissociate one from another. The receptor migrates back to the cell
surface, whereas the LDL is transported to lysosomes, where it will be degraded and its
components metabolized. This mechanism is exploited by many viruses, such as that of flu:
hemagglutinin, a MP of the viral envelope, binds to cell-surface oligosaccharides containing
sialic acids, upon which viral particles are transported to endosomes. At low pH, hemagglutinin undergoes a conformational change, exposing a hydrophobic segment that interacts with
the endosomal membrane and brings about its fusion with the viral envelope, releasing the
nucleic acid of the virus into the cytosol, where it will be transcripted and replicated. Newly
synthesized viral envelope MPs are integrated into the ER and transported to the plasma
membrane, where they bind the viral nucleic acid and its associated proteins. Viral particles
bud and are released in the extracellular medium, launching a new cycle.
• MPs are involved in transferring soluble proteins across the plasma membrane of bacteria,
across the two-membrane envelope of Gram
À bacteria, across the membrane and into the
lumen of the endoplasmic reticulum, into mitochondria and chloroplasts, etc., as well as in
integrating into one or the other target membrane newly synthesized MPs, either in the course
of their synthesis or posttranslationally (see § 1.7.1).
• Some membrane proteins are involved in structuring cells and tissues. “Band 3,” for instance,
the red blood cell anion exchanger, comprises, in addition to its TM domain, a cytosolic one
that interacts with the cytoskeleton, playing a critical role in determining the mechanical
properties of the cell. In the gap junctions, connexons integrated in the plasma membrane of
two neighboring cells not only dock one onto the other to form an aqueous channel that spans
the two plasma membranes, through which small molecules can diffuse from the cytosol of
one cell to that of the other: they also mechanically associate the two cells one with another.
This quick and somewhat shallow overview of the tasks that MPs fulfill is quite patchy, but it
gives an idea of what they must be able to achieve: form pores and regulate their specificity and their
opening; recognize, bind, and import solutes, some of them small (ions, small molecules), some very
large (proteins); transduce energy and information; associate mechanically membranes to each other or
to inside or outside structures; and carry out the budding, transport and fusion of vesicles, etc. In the
next section, we shall examine which structures have evolved to achieve such tasks. Forming a clear
view of the kinds of structure adopted by MPs and what stabilizes them is indeed essential to
understanding the problems encountered when handling them in aqueous solutions, and why certain
types of surfactants are better than others at keeping those under control.
12
1 Membrane Proteins and Their Natural Environment