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CHAPTER 6

SYSTEMSBIOLOGYOF CELLORGANIZATION

Prepared by

Brenda Leady, University of Toledo

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Systems biology

Researchers study living organisms in terms of their underlying network structure rather than their individual molecular components

The goal is to understand how the organization of the cell arises by complex interactions between its various components and parts

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All modern cells come from preexisting cell by division All cells posses a genome Living cells require pre-existing molecules Cells require pre-existing organization

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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

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Proteins often undergo protein-protein interactions

Cells must continually synthesize new molecules and break down unwanted components

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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 ATPMolecular recognition allows for complex assembly

Subunits recognize each other and bind in a specific way

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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 lifetimesHalf-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 4 stacked rings with caps in eukaryotes 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. Interior of the nucleus2. Cytosol3. Endomembrane system4. 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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Cytosol

Important coordination center Compartment for metabolism- synthesis

and breakdown Cytoskeleton found here

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Endomembrane system Secretory pathway to move substances in and

out of the cellSecretory and endocytic pathways

Membranes are dynamic and change over timeNuclear membrane during cell division

Lipids and proteins made and sorted Storage and recycling

Vacuoles and lysosomes

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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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Endomembrane system

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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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 made in the ER membrane can be transferred to other membranes by…Lateral diffusionVesicle transportLipid exchange proteins

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Palade demonstrated that secreted proteins move sequentially through organelles of the endomembrane system

Thousands of different proteins must be sorted to the correct locations

George Palade’s team used pulse-chase experiments to determine where radioactive proteins were produced and the pathways they took

Studied pancreatic cells secreting proteins Followed radioactive proteins from synthesis in the

rough ER and movements through cellular compartments

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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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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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Proteins that stay in the ER have ER retention signals

Other proteins must be sortedTransported by vesiclesVesicles incorporate coat proteinsAlso incorporates v-snare indicative of cargoT-snare on target recognizes v-snare and

vesicle fuses with target membrane

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Glycosylation

Attachment of a carbohydrate to a proteinGlycoprotein

May aid in protein folding, extracellular protection, and protein sorting

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2 forms of glycosylation

N-linkedCarbohydrate attaches to nitrogen atom of

asparagine in polypeptide chain in ER lumenOccurs in cell membrane surface proteinsRole in cell-to-cell signaling

O-linkedString of sugars attaches to oxygen of serine or

threonine in polypeptideOccurs 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 independentGenetic 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 2 traits similar to bacteria

1. Contain DNA separate from the nuclear genome

Mitochondrial and chloroplast genome Single small circular double stranded chromosome Similar to bacterial chromosomes

2. 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 speciesBeneficial for both species

Genes of mitochondria and chloroplasts 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

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Post-translational sorting

Most proteins for mitochondria, chloroplasts, and all proteins for peroxisomes sorted post-translation

Must have sorting signal Example- protein destined for

mitochondrial matrix

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