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Systems biology
The goal is to understand how the
organization of the cell arises by complex
interactions between its various
components and parts
1
All modern cells come from
preexisting cells by division
All cells posses a genome
Living cells require pre-existing molecules
Cells require pre-existing organization
2
Cell’s genetic information produces
proteome
Information in most genes is used to make
mRNA molecules that encode amino acid
sequences of proteins
Study of individual proteins does not
provide a broad integrated look at the
dynamic nature of the cell
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Genomes, proteomes and cell
structure function and organization
The proteome is largely responsible for the
structure and function of living cells
Gene and protein regulation causes the
proteome to be dynamic
Proteins have sorting signals
4
Molecular machines
A machine is an object that has moving
parts and does useful work
These machines provide structure and
organization to cells and enable them to
carry out complicated processes
ATP synthase is a molecular machine that
makes ATP
Molecular
recognition allows for complex
assembly
Subunits recognize each other and bind in a
specific way
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http://vcell.ndsu.nodak.edu/animations/atpgradient/movie.htm
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Other molecular machines
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Cytoskeleton
Key role in cell organization and many
processes that maintain the cell
Provides mechanical strength, cell shape,
organization and direction to intracellular
and cellular movements
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Molecular recycling
Large molecules, except DNA, have finite
lifetimes
Half-life
varies from 5 minutes for mRNA in
prokaryotes to 30 minutes to several days for
mRNA in eukaryotes
Continual degradation of faulty or
nonfunctional proteins and synthesis of
new ones
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Proteasome
Molecular machine for protein degradation
Ubiquitin directs unwanted proteins to
proteasomes in eukaryotes
Proteases degrade the unwanted protein
into peptides and amino acids
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Four systems work together
1.
2.
3.
4.
Interior of the nucleus
Cytosol
Endomembrane system
Semiautonomous organelles
Play a role in their own structure and in
the structure and organization of the
entire cell
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Nucleus
Genome produces the proteome that is
responsible for the structure and function of the
entire cell
Gene regulation important in creating specific
cell types and enabling response to
environmental change
Nucleus organizes itself with the nuclear matrix
Collection
of filamentous proteins
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Endomembrane system
Secretory pathway to move substances in
and out of the cell
Secretory
and endocytic pathways
Membranes are dynamic and change over
time
Nuclear
membrane during cell division
Lipids and proteins made and sorted
Storage and recycling
Vacuoles
and lysosomes
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Endomembrane system
(Nucleus, endoplasmic reticulum), Golgi
apparatus, lysosomes, vacuoles, secretory
vesicles, and plasma membrane
Reside in cytosol
Much of its activity related to transport
between compartments
Critical for lipid synthesis, protein
synthesis and sorting, and the attachment
of carbohydrates to lipids and proteins
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Semiautonomous organelles
Tend to be independent
Mitochondria make ATP
Crucial
for cell organization
Chloroplasts capture light to store energy
for later use
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Lipid synthesis
Cytosol and endomembrane system work
together to synthesize most lipids
Building blocks of phospholipids made by
enzymes in the cytosol or from the diet
Phospholipids initially made in cytosolic
leaflet but flipases in ER membrane
transfer some to the other leaflet
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Lipid transfer
Lipids found in the ER membrane can be
transferred to other membranes by…
Lateral
diffusion
Vesicle transport
Lipid exchange proteins
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Protein localization
Sorting signals or traffic signals are short
amino acid sequences that direct protein
to correct cellular location
Most eukaryotic proteins begin synthesis
(translation) on ribosomes in the cytosol
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Protein localization
Proteins that stay in the cytosol lack sorting
signals so they stay in the cytosol
Proteins for the nucleus, mitochondria,
chloroplasts, and peroxisomes occur after the
protein is made
Post-translational
sorting
Synthesis of other proteins destined for ER,
Golgi, lysosome, vacuole, plasma membrane, or
secretion halts until the ribosome is bound to the
ER
Cotranslational
sorting
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Protein localization
Proteins that stay in the ER have ER
retention signals
Other proteins must be sorted
Transported
by vesicles
Vesicles incorporate coat proteins
Also incorporates v-snare indicative of cargo
T-snare on target recognizes v-snare and
vesicle fuses with target membrane
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Glycosylation
Attachment of a carbohydrate to a protein
Glycoprotein
May aid in protein folding, extracellular
protection, and protein sorting
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2 forms of glycosylation
N-linked
Carbohydrate
attaches to nitrogen atom of
asparagine in polypeptide chain in ER lumen
Occurs in cell membrane surface proteins
Role in cell-to-cell signaling
O-linked
String
of sugars attaches to oxygen of serine
or threonine in polypeptide
Occurs only in the Golgi apparatus
Important in extracellular matrix proteins
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Semiautonomous organelles
Semiautonomous because they divide by
fission to produce more of themselves
Somewhat independent
Genetic
material, synthesize some proteins,
divide independently of cell
Do depend on the cell for raw materials
and most of their proteins
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Mitochondria and chloroplasts
1.
2 traits similar to bacteria
Contain DNA separate from the nuclear
genome
2.
Mitochondrial and chloroplast genome
Single small circular double stranded
chromosome
Similar to bacterial chromosomes
Reproduce via binary fission
Like bacteria
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Mitochondria and chloroplasts are derived
from ancient symbiotic relationships
Endosymbiosis- a smaller species lives
symbiotically inside a larger species
Beneficial
for both species
Genes of mitochondria and chloroplasts are
very similar to bacterial genes
Endosymbiosis theory
Modern
mitochondria and chloroplasts have lost
most of their genes through transfer to nucleus
Origins of peroxisomes unclear but may be
same path