Download Biochem1 2014 Recitation Chapter 11 – Lipids/Membrane Structure

Biochem1 2014 Recitation
Chapter 11 – Lipids/Membrane
Structure
What are membranes?
What is the function of the plasma membrane?
• Complex lipid-based structures that form pliable
sheets
• Composed of a variety of lipids and proteins
• Some membrane lipids and proteins are
glycosylated; glycolipids, glycoproteins &
proteoglycans
• cell membrane, which separates the cell from its
surrounding
• Eukaryotes have various internal membranes that
divide the internal space into compartments
Common Features of Membranes
• Sheet-like flexible structure, 30–100 Å (3–10 nm) thick
• Main structure is composed of two leaflets of lipids (bilayer)
– With the exception of archaebacteria: monolayer of bifunctional lipids
• Form spontaneously in aqueous solution and are stabilized by
noncovalent forces, especially hydrophobic effect
• Protein molecules span the lipid bilayer
• Asymmetric
– Some lipids are found preferably “inside”
– Some lipids are found preferably “outside”
– Carbohydrate moieties are always outside the cell
– Electrically polarized (inside negative ~ –60mV)
• Fluid structures: two-dimensional solution of oriented lipids
The Fluid Mosaic Model: Details
Fluid mosaic model for plasma membrane structure. The fatty acyl chains
in the interior of the membrane form a fluid, hydrophobic region. Integral
proteins float in this sea of lipid, held by hydrophobic interactions with their
nonpolar amino acid side chains. Both proteins and lipids are free to move
laterally in the plane of the bilayer, but movement of either from one leaflet
of the bilayer to the other is restricted. The carbohydrate moieties
attached to some proteins and lipids of the plasma membrane are exposed on
the extracellular surface.
Membrane composition is
highly variable in different organisms
Membrane composition is
highly variable in different organelles
•
Lipid composition of the plasma membrane and
organelle membranes of a rat hepatocyte. The
functional specialization of each membrane type is
reflected in its unique lipid composition. Cholesterol is
prominent in plasma membranes but barely detectable
in mitochondrial membranes. Cardiolipin is a major
component of the inner mitochondrial membrane but
not of the plasma membrane. Phosphatidylserine,
phosphatidylinositol, and phosphatidylglycerol are
relatively minor components of most membranes but
serve critical functions; phosphatidylinositol and its
derivatives, for example, are important in signal
transductions triggered by hormones. Sphingolipids,
phosphatidylcholine, and phosphatidylethanolamine are
present in most membranes but in varying proportions.
Glycolipids, which are major components of the
chloroplast membranes of plants, are virtually absent
from animal cells.
Membrane bilayers are asymmetric
Asymmetric distribution of
phospholipids between the
inner and outer monolayers of
the erythrocyte plasma
membrane. The distribution of a
specific phospholipid is
determined by treating the intact
cell with phospholipase C, which
cannot reach lipids in the inner
monolayer (leaflet) but removes
the head groups of lipids in the
outer monolayer. The proportion
of each head group released
provides an estimate of the
fraction of each lipid in the outer
monolayer.
Three Types of Membrane Proteins
•
Peripheral, integral, and amphitropic proteins.
Membrane proteins can be operationally distinguished
by the conditions required to release them from the
membrane. Most peripheral proteins are released by
changes in pH or ionic strength, removal of Ca2+ by a
chelating agent, or addition of urea or carbonate.
Integral proteins are extractable with detergents, which
disrupt the hydrophobic interactions with the lipid
bilayer and form micelle-like clusters around individual
protein molecules. Integral proteins covalently attached
to a membrane lipid, such as a glycosyl
phosphatidylinositol (GPI; see Fig. 11–15), can be
released by treatment with phospholipase C.
Amphitropic proteins are sometimes associated with
membranes and sometimes not, depending on some
type of regulatory process such as reversible
palmitoylation.
Six Types of Integral
Membrane Proteins
For known proteins, the spatial relationships of protein domains
to the lipid bilayer fall into six categories. Types I and II have a
single transmembrane helix; the amino-terminal domain is
outside the cell in type I proteins and inside in type II. Type III
proteins have multiple transmembrane helices in a single
polypeptide. In type IV proteins, transmembrane domains of
several different polypeptides assemble to form a channel through
the membrane. Type V proteins are held to the bilayer primarily
by covalently linked lipids, and type VI proteins have both
transmembrane helices and lipid
Amino acids in membrane proteins
cluster in distinct regions
•
Transmembrane segments are predominantly hydrophobic
•
Tyr and Trp cluster at nonpolar/polar interface
•
Charged amino acids are only found in aqueous domains
Tyr and Trp residues of membrane proteins clustering at the water-lipid interface. The
detailed structures of these five integral membrane proteins are known from
crystallographic studies. The K+ channel (PDB ID 1BL8) is from the bacterium
Streptomyces lividans; maltoporin (PDB ID 1AF6), outer membrane phospholipase A
(OmpLA, PDB ID 1QD5), OmpX (PDB ID 1QJ9), and phosphoporin E (PDB ID 1PHO)
are proteins of the outer membrane of E. coli. Residues of Tyr and Trp are found
predominantly where the nonpolar region of acyl chains meets the polar head group region.
Charged residues (Lys, Arg, Glu, Asp) are found almost exclusively in the aqueous phases.
Membrane proteins also contain -sheets
Membrane proteins with -barrel structure. Three proteins of the E.
coli outer membrane are shown, viewed in the plane of the membrane.
FepA (PDB ID 1FEP), involved in iron uptake, has 22 membrane
spanning β strands. OmpLA (derived from PDB ID 1QD5), a
phospholipase, is a 12-stranded β barrel that exists as a dimer in the
membrane. Maltoporin (derived from PDB ID 1MAL), a maltose
transporter, is a trimer; each monomer consists of 16 β strands.
Membrane Rafts
Lipid distribution in a single leaflet is not random or uniform
• Lipid rafts
– contain clusters of glycosphingolipids with longer-than-usual tails
– are more ordered
– contain specific doubly or triply acylated proteins
– allow segregation of proteins in the membrane
•
Membrane microdomains (rafts). Stable
associations of sphingolipids and cholesterol
in the outer leaflet produce a microdomain,
slightly thicker than other membrane regions,
that is enriched with specific types of
membrane proteins. GPI-anchored proteins
are prominent in the outer leaflet of these
rafts, and proteins with one or several
covalently attached long-chain acyl groups
are common in the inner leaflet. Inwardly
curved rafts called caveolae are especially
enriched in the protein caveolin. Proteins
with attached prenyl groups (such as Ras)
tend to be excluded from rafts.
Caveolin forces membrane curvature
•
Caveolin forces inward curvature of a
membrane. Caveolae are small invaginations in
the plasma membrane, as seen in (a) an
electron micrograph of an adipocyte that is
surface-labeled with an electron-dense marker.
(b) Cartoon showing the location and role of
caveolin in causing inward membrane
curvature. Each caveolin monomer has a central
hydrophobic domain and three long-chain acyl
groups (red), which hold the molecule to the
inside of the plasma membrane. When several
caveolin dimers are concentrated in a small
region (a raft), they force a curvature in the
lipid bilayer, forming a caveola. Cholesterol
molecules in the bilayer are shown in orange.
Polar solutes need alternative paths to
cross cell membranes
Energy changes accompanying passage
of a hydrophilic solute through the lipid
bilayer of a biological membrane. (a) In
simple diffusion, removal of the hydration
shell is highly endergonic, and the energy of
activation (∆G‡) for diffusion through the
bilayer is very high. (b) A transporter protein
reduces the ∆G‡ for transmembrane diffusion
of the solute. It does this by forming
noncovalent interactions with the dehydrated
solute to replace the hydrogen bonding with
water and by providing a hydrophilic
transmembrane pathway.
Three Classes of Transport Systems
Three general classes of transport systems. Transporters differ in the
number of solutes (substrates) transported and the direction in which each
solute moves. Examples of all three types of transporter are discussed in the
text. Note that this classification tells us nothing about whether these are
energy-requiring (active transport) or energy-independent (passive transport)
processes.