Transcript BIO 121

BIO 121 – Cell Physiology
Lecture Section II
A. Biological Membranes
B. Protein Structure and Function
C. The Cytoskeletal System and Adhesion
D. Cellular Movements
E. The Endomembrane System
and Intracellular Trafficking
1. Review of the Fundamental Structures
and Functions of Biological Membranes
All cells have a plasmamembrane,
eukaryotes have maximized use of
membranes
The membranes and membrane-bound
compartments of eukaryotic cells allow for
the far greater complexity of structure and
function in those cells
Prokaryotes:
Cytoplasm bound by plasma membrane, no organelles
No nucleus, DNA in an unbound region called the nucleoid
Nucleoid
Plasma membrane
Bacterial
chromosome
Cell wall
The plasma membrane is a selective
barrier that allows sufficient passage of
oxygen, nutrients, and waste to service
the volume of every cell
Nuclear
envelope
Typical
animal
cell
Rough ER
Smooth ER
Plasma
membrane
CYTOSKELETON:
Microfilaments
Intermediate
filaments
Microtubules
Golgi
apparatus
Mitochondrion
Lysosome
Fig. 6-9b
Nuclear envelope
Rough endoplasmic
reticulum
Plant and animal
cells have most of
the same organelles
Smooth endoplasmic
reticulum
Central vacuole
Golgi
apparatus
Microfilaments
Intermediate
filaments
Microtubules
CYTOSKELETON
Mitochondrion
Chloroplast
Plasma
membrane
Cell wall
Plasmodesmata
Wall of adjacent cell
Same for fungi
and protists.....
The Eukaryotic Membrane System
• Components of the membrane system:
• Plasma membrane
• Nuclear envelope
• Endoplasmic reticulum
• Golgi apparatus
• Mitochondria and Chloroplasts
• Lysosomes
• Peroxisomes
• Vacuoles
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
b. The main components of membrane structure
are ......
» The Amphipathic Lipid Bilayer
» Membrane Proteins and Sugars
» The Cytosolic Submembrane Protein Meshwork
Fig. 7-2
The Amphipathic Lipid Bilayer
The most fundamental structure of a biological
membrane is a double layer of phospholipids
WATER
Hydrophilic
head
Hydrophobic
tail
WATER
There are many types of phospholipids
Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)
Glycolipids
Figure 10-18 Molecular Biology of the Cell (© Garland Science 2008)
Figure 10-5 Molecular Biology of the Cell (© Garland Science 2008)
Fig. 7-5b
•Membranes must be fluid to work properly
• they are usually about as fluid as salad oil
•Membranes rich in unsaturated fatty acids are more fluid that those rich in
saturated fatty acids
Fluid
Unsaturated hydrocarbon
tails with kinks
Viscous
Saturated hydrocarbon tails
Fig. 7-5c
•The steroid cholesterol has different effects on membrane fluidity at different
temperatures
•At warm temperatures (such as 37°C), cholesterol restrains movement of
phospholipids
•At cool temperatures, it maintains fluidity by preventing tight packing
Cholesterol
Membrane
lipids provide
hydrophobic to
most molecules
dissolved in
water and allow
a select few to
diffuse across
-oxygen
-carbon dioxide
-urea
-water
Figure 10-9b Molecular Biology of the Cell (© Garland Science 2008)
Spontaneous
formation
and ‘healing’
The Permeability of the Lipid Bilayer
Hydrophobic (nonpolar) molecules, such as hydrocarbons, can
dissolve in the lipid bilayer and pass through the membrane
rapidly
estradiol
Charged or strongly polar
molecules, such as ions,
sugars and proteins, do
not cross the membrane easily
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
testosterone
glucose
proteins
Fig. 7-13
Hypotonic solution
H2O
Isotonic solution
Hypertonic solution
H2O
H2O
H2O
(a) Animal
cell
Lysed
H2O
Normal
Shriveled
H2O
H2O
H2O
(b) Plant
cell
Turgid (normal)
Flaccid
Plasmolyzed
Membrane proteins provide the bulk of specific membrane
functions and their variation is a primary determinant of
cellular identity
Proteins can associate with membranes in a variety of ways:
Transmembrane Proteins
1. single pass
2. multiple pass
3. barrel or channel
4. single
sheath
proteins
Figure 10-19 Molecular Biology of the Cell (© Garland Science 2008)
Anchored Proteins
5. lipid anchor
6. sugar anchor
7/8 protein anchor
Protein-lipid ratio varies hugely in
different membranes
1. myelin sheath
2. outer mitochondrial
3. inner mitochondrial
protein
20%
50%
80%
lipid
80%
50%
20%
Fig. 7-9ac
Typical functions of membrane proteins
Signaling molecule
Enzymes
ATP
(a) Transport
Receptor
Signal transduction
(b) Enzymatic activity
(c) Signal transduction
Fig. 7-9df
Glycoprotein
(d) Cell-cell recognition
(e) Intercellular joining
Carbohydrates often play important roles on
the plasma membrane. Covalently bonded to
lipids (forming glycolipids) or more commonly
to proteins (forming glycoproteins)
(f) Attachment to
the cytoskeleton
and extracellular
matrix (ECM)
Biochemical structure depends on surroundings
EXTRACELLULAR
SIDE
N-terminus
What
types
of
side
chains
are on
outside
of
these
helices?
C-terminus
 Helix
CYTOPLASMIC
SIDE
Fig. 7-17
Passive transport
Active transport
ATP
Diffusion
Facilitated diffusion
Nutrient uptake
Waste elimination
pH and osmolarity maintenance
Electrical gradient maintenance
We have pumps for glucose, amino acids,
calcium, and many other molecules
Figure 11-12 Molecular Biology of the Cell (© Garland Science 2008)
Sugars are found on the non-cytosolic face of membranes
Figure 10-28b Molecular Biology of the Cell (© Garland Science 2008)
Review of Membrane Structure
The third component: submembrane protein meshwork
Always on the cytosolic face
Allows membrane to communicate with the rest of the cell
Figure 10-41a Molecular Biology of the Cell (© Garland Science 2008)
A major role of the meshwork is to segregate and
establish functional domains in the membrane
Figure 10-42 Molecular Biology of the Cell (© Garland Science 2008)
Some Structures that Live in
the Submembrane Meshwork:
- Membrane identification proteins
- Anchor proteins for cadherins and integrins
- 2nd messengers for signaling pathways
- Ribosome docking proteins
- Chaperonin docking proteins
What are the Principle Functions of
Cell Membranes?
• Compartmentilization of Cell Functions
• Defense and Integrity of Cellular or Compartmental Contents
• Selective Permeability in Two Directions
• Regulation of Internal Cellular or Compartmental Activities
• Attachment and Movement of the cell or Compartment
• Response to Signals from Outside of the Cell or Compartment
Table 12-2 Molecular Biology of the Cell (© Garland Science 2008)
Key Functions of the Nucleus and
Endoplasmic Reticulum
• Store, protect and transcribe the DNA
• Deliver RNAs for translation
• Lipid biosynthesis and protein translation
• Integration of membrane lipid and protein
• Detoxification of dangerous materials
• Calcium sequestration
Figure 12-8 Molecular Biology of the Cell (© Garland Science 2008)
rRNA Production
mRNA Production
Nuclear Pore Complex
Figure 12-9a Molecular Biology of the Cell (© Garland Science 2008)
Translation and Lipid Synthesis
Key Functions of the Golgi Apparatus (GA)
1. Post-translational modification of membrane
lipid and protein constituents.
a. Sulfation, glycosylation, adenylation,
phosphorylation, etc.
2. Membrane Targeting. Control of the cellular
destinations of prepared membrane and protein
vesicles.
Figure 13-28 Molecular Biology of the Cell (© Garland Science 2008)
Functions of Mitochondria and Chloroplasts
1. Captive energy
plants for the cell
2. Store, protect,
express their own
DNA
Key Functions of the Endosomal System
Figure 13-42a Molecular Biology of the Cell (© Garland Science 2008)
Recycling of
membrane
components
Figure 13-53 Molecular Biology of the Cell (© Garland Science 2008)
Key Functions of the Peroxisome
Key Functions of the Vacuole
Control of water and ion
exchange is organisms
dependent on a variable
external environment
B. Protein Structure and Function
Protein biochemistry dictates their
functional activities
Regulation of protein structure and
function is one of the most fundamental
means by which cells control their own
activities
a. Final amino acid position results from the
conformation that gives the lowest free energy
most of this is driven
by the polar aqueous
and non-polar
membrane phases
Figure 3-1 (part 2 of 2) Molecular Biology of the Cell (© Garland Science 2008)
In the aqueous phase polar side chains
face out, in the membrane they are hidden
Figure 3-5 Molecular Biology of the Cell (© Garland Science 2008)
Many forces help maintain the final shape
Figure 3-4 Molecular Biology of the Cell (© Garland Science 2008)
Self- and regulated- assembly of large structures
hemoglobin is made
up of 2 alpha and
2 beta subunits
Figure 3-22 Molecular Biology of the Cell (© Garland Science 2008)
Collagen fibrils are made up of many collagen proteins,
each of which are made of 3 collagen subunit peptides
Figure 3-27a Molecular Biology of the Cell (© Garland Science 2008)
Because of gene duplication and exon duplication modularity
of structure is common: Protein families and domains
Two serine protease genes give nearly exact binding site structure
Figure 3-12 Molecular Biology of the Cell (© Garland Science 2008)
Final Structure = Final Function
Active amino acids
widely distributed
Folding places them into
active distribution
Fig. 7-16-1
Binding changes protein conformation,
change in conformation alters activity
EXTRACELLULAR FLUID
Example:
The sodiumpotassium
pump
Na+
[Na+] high
[K+] low
Na+
CYTOPLASM
Na+
1
Cytoplasmic Na+ binds
[Na+] low
[K+] high
Fig. 7-16-2
Na+
Na+
Na+
P
ADP
2
ATP
Na+ binding stimulates
phosphorylation by ATP.
Fig. 7-16-3
Na+
Na+
Na+
P
3
Phosphorylation causes the
protein to change its shape.
Na+ is expelled to the outside.
Fig. 7-16-4
P
4 K+ binds on the
extracellular side and
triggers release of the
phosphate group.
P
Fig. 7-16-5
5 Loss of the phosphate
restores the protein’s original
shape.
Fig. 7-16-6
K+ is released, and the
cycle repeats.
Why do we want Na+ outside of the cell and K+ inside?
Cells can control protein activity
directly by mechanisms that
target the protein itself
Definition: “Allosteric”. Proteins with two or more
binding sites, wherein activity away from the active
site will regulate activity at the active site
Figure 3-58 Molecular Biology of the Cell (© Garland Science 2008)
Figure 3-59 Molecular Biology of the Cell (© Garland Science 2008)
phosphorylation-dephosphorylation
1. Cells can start
and stop a protein’s
activity by changing
its structure
through the
addition of a
covalent subgroup
Figure 3-64 Molecular Biology of the Cell (© Garland Science 2008)
glycosylation
Figure 12-51 Molecular Biology of the Cell (© Garland Science 2008)
Addition of covalently linked lipids allows a protein
to have a tight association with the membrane
Figure 10-20 Molecular Biology of the Cell (© Garland Science 2008)
Complex Covalent Regulation
of the p53 Transcription Factor
Figure 3-81a Molecular Biology of the Cell (© Garland Science 2008)
Figure 3-81c Molecular Biology of the Cell (© Garland Science 2008)
2. Cells can start and stop a
protein’s activity by
proteolytic cleavage
Figure 3-35 Molecular Biology of the Cell (© Garland Science 2008)
The clotting cascade is the same
Figure 18-5a Molecular Biology of the Cell (© Garland Science 2008)
3. Some regulatory mechanisms involve multiple
strategies such as activation of Src protein
Figure 3-69 (part 1 of 3) Molecular Biology of the Cell (© Garland Science 2008)
Figure 3-69 (part 2 of 3) Molecular Biology of the Cell (© Garland Science 2008)
Figure 3-69 (part 3 of 3) Molecular Biology of the Cell (© Garland Science 2008)
Cells can control protein activity
indirectly by altering the other
molecules that share its
environment
1. Cells can start and stop a protein’s activity by
regulating the presence of a critical binding partner
a. Ligand interaction
activates receptor
Figure 15-53a Molecular Biology of the Cell (© Garland Science 2008)
2. Sequestration of effector molecules
linked to controlled release
eg. Hide all of the calcium until you
want to change actin-myosin activity
Figure 11-12 Molecular Biology of the Cell (© Garland Science 2008)
c. Cooperative/Coupled binding - Substrate binding in one site
effects binding of substrate in second site by changing affinity
Hemoglobin binds oxygen
with greater affinity when
there is lots of oxygen – this
ensures flow of oxygen to
the tissues and not away.
2. Cells can start and stop a protein’s activity
by blocking its binding site
Tropomyosin blocking the
myosin-binding site on actin
Figure 16-78a Molecular Biology of the Cell (© Garland Science 2008)
3. Cells can start and stop a protein’s activity by
regulating the processes that make active polymers
from inactive subunits
Figure 17-49a Molecular Biology of the Cell (© Garland Science 2008)
4. Cells can start and stop a protein’s activity by regulating the
scaffolded interaction of the subunits of protein machines
Ubiquitin
ligase
complex
Figure 3-79 Molecular Biology of the Cell (© Garland Science 2008)
Synaptic
scaffold
Figure 19-21 Molecular Biology of the Cell (© Garland Science 2008)
Figure 15-21a Molecular Biology of the Cell (© Garland Science 2008)
Sometimes the scaffold protein is
even part of the signaling cascade!
Figure 15-61 Molecular Biology of the Cell (© Garland Science 2008)