Chapter 5: Systems Biology of Cell Organization

o Describe the relationship of the macromolecules DNA, RNA, and protein to the terms genome

and proteome.

DNA gets transcribed into RNA and then RNA gets translated into a protein. An organism’s genome is

its complete collection of DNA and from that DNA, specific cells make specialized proteins that

perform different functions which make up the proteome.

o Understand how the unifying biological principle that structure determines function is

particularly important in creation of molecular machines.

A protein is considered a machine because it undergoes conformational change to perform a

function. Has moving parts and does useful work. In proteins, shape dictates function because if a

protein doesn’t have a specific shape to bind to a receptor, then that process will not occur.

Molecular machines are vital in promoting cell organization. The cytoskeleton is involved in the

organization of the cytosol. Although some molecular machines can assemble spontaneously from

their components, the complex interacting machinery of the cell is so complex that it needs existing

structure to guide assembly of the new components. Thus we can see why one biological principle is

that all cells originate from existing cells

o Describe how a eukaryotic cell can be viewed as four interacting systems: the nucleus, cytosol,

endomembrane system, and semiautonomous organelles.

Nucleus – houses a cell’s DNA and its processes include protection, replication and packaging for cell

division. It is also the site of transcription.

Cytosol – coordinates a response to the environment, metabolism and motor proteins

Endomembrane system – includes the nuclear envelope (surrounds nucleus), rough and smooth ER,

golgi body, lysosomes/vacuoles, peroxisome and plasma membrane.

Semiautonomous organelles – mitochondria (animals) and chloroplast (plants) which provide energy

for the cell.

o Create a labelled diagram describing the flow of information from the nucleus, to the cytoplasm,

to the environment, to the cytoplasm, and back to the nucleus, and label key structures and

molecules.

o Name the particular RNA molecules that are intermediates for producing the proteome, and

indicate which proteins are important decision makers in producing these RNA molecules.

The particular RNA molecules that produce the proteome are mRNA, tRNA and rRNA. They are all

created in the nucleus, exit through the nuclear pores and enter the cytoplasm to function in

translation. Specific amino acids join together to create a polypeptide and once this is created, the

polypeptide must fold into its proper shape and get to the correct part of the cell to become a

functional protein. When proteins reach their destination they create the foundation for cell

structure, function and organization by providing structural proteins, transport proteins, extracellular

proteins, signaling proteins and enzymes.

Transcriptional factors – the proteins that help determine which parts of the genome will be

selected for transcription.

o Justify thinking of the outer leaflet of the cell membrane as an important part of the cell.

The outer leaflet is a phospholipid bilayer. The outer leaflet is very important because it is the part of

the cell that interacts with the outside environment

o List the categories of proteins that are sorted cotranslationally and those that are sorted post-

translationally.

- Membrane proteins are sorted cotranslationally into the ER and contain a signal recognition

particle that is inserted via translation

- Proteins needed in the nucleus, peroxisomes, mitochondria, or chloroplasts enter sorting

post-translationally

• Proteins that stay in the cytosol lack sorting signals

• Sorting to nucleus, mitochondria, chloroplasts, and peroxisomes (some) occur after the protein is made – Post-translational sorting

- For post translational sorting to occur the protein must contain a specific amino acid

sequence called a targeting signal that directs that protein to its desired location

o Describe the steps that occur during the cotranslational sorting of proteins to the endoplasmic

reticulum.

The steps include:

1) Sorting begins in the transcription phase when the ER signal peptide is created and attaches

the signal recognition particle (SRP) which pauses transcription (ER signal sequence is where

the “postal code” is)

2) The SRP moves the entire complex (mRNA, ribosomes and emerging signal peptide) to the ER

membrane

3) The ribosome opens the protein channel and provides passages to the lumen of the ER. SRP

releases

4) The growing peptide threads through the channel and eventual the ER signal sequence is

cleaved

5) Polypeptide is released into the lumen of the ER

o Explain how proteins are moved via vesicles through the endomembrane system.

If there is no ER retention, then vesicles transport (Proteins that stay in the ER have ER retention

signals in addition to ER signals this doesn’t so proteins must be transported by vesicles and these

vesicles incorporate coat proteins for specificity and incorporate v-snares that indicate for certain

cargo t-snare on targer recognizes v-snare and vesicle fuses with target membrane)

- Proteins coming from the lumen of the ER are always encased in vesicles

• 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

- Protein molecules bind to the cargo receptors which stimulates the binding of a cage-like

shell which helps the membrane bud from the vesicle (this handshake will only happen

between golgi and the vesicle because of proper recognition between the 2)

o Outline the steps of post-translational sorting of proteins to mitochondria or chloroplasts.

This is after polypeptide is made most proteins for mito, chloro and all proteins for peroxisomes

are sorted post-translationally they must have a sorting signal)

- Chaperone proteins keep protein unfolded so the mitochondria sorting signal can bind

- The protein releases the chaperones and enters the outer and inner membrane via channels

- Chaperones bind again in the matrix

- The sorting signal is cleaves and the protein is threaded into matrix

- Chaperones release and protein folds into tertiary structure.

o Describe the proteasome-based process of protein degradation. Explain the purposes of the

proteosome system. Contrast the proteosome degradation system with that of the lysosome.

- To degrade proteins proteasomes are

enzymes that cleave the bonds between

amino acids they are also considered

molecular machines

- Ubiquitin (most common flag to degrade

proteins) recognizes if the protein is

necessary or unnecessary and targets

unnecessary proteins to the proteasome

also can target misfolded proteins

- Proteasomes degrade proteins into small

peptides or amino acids and recycle them

back into the cytosol

- In the cytosol those cleaved amino acids

are used to make new proteins

- Lysosomes can also degrade materials in

the cytosol or degrade proteins that enter

the cell in endocytosis

o Describe the major events proposed to

account for the evolution of the double-

membrane organelles: the nucleus,

mitochondria, and chloroplasts.

- it is said that the mitochondria and chloroplasts are derived from ancient symbiotic

relationships (symbiosis occurs when 2 different species live in direct contact with each other

and benefit)

- Endosymbiosis is when the smaller organism lives inside the larger one

- Scientists believe the mitochondria, chloroplasts and nucleus were once their own organism

that decided to reside inside a cell and over time that cell evolved to include those organelles

this is why these organelles contain separate membranes and are semi-autonomous

o Discuss the evidence for the endosymbiosis theory.

From this theory it is proposed that mitochondria are derived from purple bacteria and chloroplasts

from cyanobacteria proof: a. Have a double membrane – outer membrane has eukaryotic orgin and inner membrane

has prokaryotic origin b. Have a single loop of DNA c. Reproduce by binary fission d. Have ribosomes but are of prokaryotic origin e. About the same size as prokaryotes

o Explain the functional roles of the extracellular matrix in animals. (don’t put too much emphasis

in the studying of this and everything else below this)

- The ECM in animals serves a similar role to the cell wall in plants it allows certain cells to

adhere to the ECM on only one side

- It provides support, strength, organization and cell signaling

- The tough stuff on animal cells (i.e. shells) are the ECM

- The skeleton of animals are composed of the ECM

- The attachment of cells to the ECM promotes organization

- Cell signaling is how organisms interact with environment and is controlled by the ECM

o Describe the structure and function of plant cell walls.

- It is a protective layer that forms outside the plasma membrane of the plant cell and is

composed of the primary and secondary cell wall (primary made before)

- The main component of the primary cell wall is cellulose and made to grow with the cell

- The secondary cell wall is created after the cell has finished growing

o Outline the structure and function of anchoring junctions, tight junctions and gap junctions.

- Anchoring junctions play a role in anchoring cells to one another or in the extracellular matrix

- Tight junctions seal cells together into a tissue that prevents small molecules from leaking

through one cell layer to another

- Gap junctions allow cells to communicate directly with each other

o Describe the structure and function of middle lamella and plasmodesmata

- Middle lamella is a call junction in plants and is the first layer to divide it is also rich in

pectin, which is negatively charged carbohydrate polymers

- The primary cell wall is made in the middle lamella

- Middle lamella forms a hydrated gel with Ca2+ and Mg+2

- Plasmodesmata allow the passage of ions, water, sugars, amino acids and signaling

molecules between cells opens the channels in the cell wall

- At these channels, the plasma membrane of one cell is continuous with another cell

o Explain whether cells of the same tissue have identical or similar genomes and proteomes.

All cells in the same organism have the same genome. However, cells of the same tissues have the

same proteome and are unique to other tissues. Proteomes vary amoung tissues because they all

form unique functions.

Genome, Proteome and the Environment

DNA > RNA > Protein

genome is organisms complete collection of hereditary material (individual units=genes)

genes used as templates to make RNA in transcription

tRNAs and rRNAs assist production of polypeptides in translation

Structure in Cells

• Molecular machine: machines whose sizes are measured in nanometers and have moving parts and do useful

work

• molecular machines can associate with one another and with nucleic acids to form more complex machines

• sometimes additional proteins needed for functioning of molecular machine

• some machines require energy input

• ATP synthase is compose of subunits a, b, c, alpha, beta, gamma, delta, and epsilon

• a, b and c subunits are transmembrane proteins

• 9-12 c subunits form ring in membrane, and 1 a and two b subunits bind to ring

• other subunits form complex of 3 beta, 3 gamma, 1 alpha, 1 delta, and 1 epsilon

• binds to membrane components

• amino acid sequence of each of these subunits folds and interlocks when assembling with others

• ribosome is composed of many protein types and large RNAs (polypeptide synthesis)

• flagellum is composed of microtubules, motor proteins, and other proteins (locomotion)

• cytoskeleton is a molecular machine providing cell organization

4 Major Compartments of Cells

1. interior of nucleus

2. cytosol

3. semiautonomous organelles

4. endomembrane system

Nucleus as Site of Genome to Proteome Decisions

• most reactions in nucleus are for protecting DNA from damage, replicating and packaging it for cell division,

using DNA to make RNA, and processing RNA

• transcription- DNA used to make RNA (occurs in nucleus because DNA does not leave the nucleus)

• translation- RNA used to make protein (occurs in cytoplasm)

• mRNA, tRNA, and rRNA made in nucleus and exit through nuclear pores for translation

• rRNA only leaves nucleus when partnered with proteins to form ribosomal subunits (combine with

mRNA)

• mRNA encodes for information to make polypeptide (decoded in translation with help of tRNA)

• once made, proteins fold into proper shape and become functional

• some proteins made in cytosol function in nucleus for DNA repair, DNA replication, DNA packaging, RNA

transcription, and RNA processing

• transcription factors: proteins that help determine which parts of the genome will be selected for

transcription

• recognize and bind to target gene, which will be expressed (transcribed)

Cytosol

• coordination centre for cell function and organization

• components coordinate responses to environment

(along with plasma membrane)

• major site for translation

• compartment where many small molecules are

metabolized

• pathways for synthesis and breakdown of cellular

molecules found in cytosol

• organized by cytoskeleton

• intermediate filaments- mechanical strength

• actin filaments- protein network on inner

plasma membrane for anchoring

proteins

• membrane proteins help interact

with environment

• protein-protein interactions occur between actin and other proteins to produce changes

• provides pathways for directed intracellular movement of vesicles, chromosomes and mitochondria

Semiautonomous Organelles

• mitochondria and chloroplasts

• found in cytosol

• operate simultaneously

• each contains their own genetic material and divide by binary fission

• chromosomes in mitochondria and chloroplasts make up mitochondrial genome and chloroplast genome

• much smaller than nuclear genome

• production of new mitochondria and chloroplasts is similar to division of bacterial cells

• vital energy-generating systems with dual-origin proteomes

• involved in energy conversions

• contain some organelle-encoded polypeptides, but majority are from nucleus

Endomembrane System

• includes outer membrane of nuclear envelope, endoplasmic reticulum, Golgi, lysosomes, peroxisomes,

vacuoles, secretory vesicles, and plasma membrane

• activity related to transport of membrane vesicles (endocytosis/exocysosis)

• structure and organization

• major site of metabolic reactions

• most lipids made in ER membrane

• proteins synthesized in ER

• storage (vacuoles) and recycling (lysosomes) of organic molecules

• peroxisomes metabolize some fats and amino acids

• routing system for transporting proteins to final destination

• phospholipid bilayer (outer and inner leaflets)

• outer leaflet faces exterior

• inner leaflet faces cytosol

• works with cytosol to create most lipids

• occurs at ER membrane's cytosolic leaflet (faces cytosol)

• in cytosol, fatty acids are activated by attachment of CoA molecule

• activated fatty acids bond to glycerol-phosphate and are inserted into cytosolic leaflet of ER

membrane via the enzyme acyl transferase

• phosphate removed by phosphatase enzyme

• a molecule of choline already linked to phosphate is attached via choline phosphotransferase

• flippases transfer some of phospholipids to other leaflet

• proteins found in all types of membranes (important roles)

Sorting Proteins to Cellular Compartments

• nuclear-encoded polypeptides have a short stretch of amino acids that helps direct them to correct location

• sequences called sorting signals or traffic signals

• created in translation

• signal peptide: part of polypeptide (6-12 amino acids) that serves to direct polypeptide to specific cell

compartment

Polypeptides Directed to ER

• proteins travelling through endomembrane system require ER signal peptide

1. SRP (signal recognition particle) binds to ER signal sequence and pauses translation

2. SRP binds to receptor in ER membrane

3. SRP is released, translation resumes, and growing polypeptide threads into channel

4. ER sorting signal peptide is usually cleaved by signal peptidase

5. polypeptide is completely synthesized and released into ER lumen

• most membrane proteins are inserted into the ER membranes cotranslationally

• amino acids of membrane proteins' ER signal peptide are not always removed

1. when they are not removed, they embed into lipid bilayer because they are hydrophobic

• all membrane proteins have at least one stretch of amino acids that are mostly hydrophobic

• some polypeptides may consist of two or more transmembrane segments (each 20 hydrophobic amino acids)

• once in ER membrane, protein can be transported to other membranes of endomembrane system via

vesicles

• proteins released into ER lumen can have different final destinations and different modifications

• in lumen of ER, many proteins have carbohydrate groups covalently linked to certain amino acids

1. called glycosylation

2. proteins destined for lysosome

receive specific type of

glycosylation serving as an

additional sorting signal

3. alters physical properties of proteins (may make it

more stable)

4. can be important to protein's ability to perform

5. proteins secreted from cell are often extensively

glycosylated (proteoglycans)

Degrading and Recycling Macromolecules

• lysosomes can degrade materials in cytosol through

autophagy (mitochondrial components, proteins)

• cytosolic enzymes break down RNA, polysaccharides, and

lipids (i.e., ribonuclease)

• cells must continually degrade faulty/nonfunctional

proteins and replace them

• cells also sometimes need to degrade functional proteins

• to be degraded, proteins recognizes by proteases (enzymes that cleave bonds between amino acids)

• proteasome: primary pathway from protein degradation (machine)

• formed from 4 stacked rings, each with 7 protein subunits

• contain cap structures at each end to control entry of proteins and exit of amino acids

• a string of ubiquitins is attached to a protein, directing it to proteasome

• protein is unfolded by enzymes in cap and injected into core proteasome. ubiquitin is released back

into cytosol

• protein is degraded to small peptides and amino acids

• small peptides and amino acids are recycled back to cytosol

• ubiquitin targeting has two main uses

• enzymes that attach ubiquitin to target recognize improperly folded proteins, allowing cells to

identify and degrade nonfunctional components

• changes in cellular conditions may warrant rapid breakdown of particular cells, and ubiquitin

targeting directs proteins that cause these conditions to proteasome for degradation

Cells as the Building Blocks of Multicellular Organisms

• multicellularity is in some protists and fungi, and all plant and animal kingdoms

• tissues: clusters of cells within an organism with similar structure and function

• fundamental unit in multicellular organisms

• cells are organized into tissues, and tissues are organized into organs

• organ: a collection of two or more tissues that performs a specific function or set of functions (i.e., heart, leaf)

• six processes involved in making tissues that influence their morphology, arrangement, and number:

• cell division: cell cycle leads to cell division

• cell growth: cells take up nutrients and usually expand in volume

• differentiation: during development, cells differentiate into specialized types of cells (results from

changes in proteome, and is driven by differential expression of genome)

• migration: during embryonic development in animals, cells migrate to their appropriate positions

within the body (does not occur during plant development)

• apoptosis: programmed cell death is a regulated and normal feature of plant and animal

development, and is necessary o produce certain morphological features of the body (i.e.,

removal of skin cells to form fingers and toes)

• cell connections: ECM organizes cells within tissues and organs in animals, and the cell wall forms the

ECM that shapes plant tissues