Week 2 Textbook Reading

Question 1

amino acid structure

Answer 1

All amino acids have the same basic underlying structure
Every AA has an alpha carbon to which all the other atoms and groups are attached
Every AA also has a carboxyl group which is OH-C=O

Question 2

What differentiates AA is their R group

Answer 2

The R groups are the side chains and makes each AA unique
The linear order of how the AA are connected together is what gives rise to each unique protein

Question 3

how is a peptide bond formed?

Answer 3

To form a peptide bond, there is a reaction between the carboxyl group and the amino group
R groups not involved in polypeptide formation
Rxn produces Amino end (N-terminus) and Carboxyl end (C-terminus)

Question 4

how is a polypeptide chain formed?

Answer 4

Addition of AA and formation of peptide bonds is repeated until polypeptide chain is complete
While, maintaining polarity and directionality of the polypeptide
This is the primary structure

Question 5

alpha helix

Answer 5

-secondary structure

-Backbone of alpha helix has a amino or N-terminal end and a carboxyl or C-terminal end

One AA are joined together into a polypeptide chain, now referred to as residues

Hydrogen bonding between an oxygen atom of the carbonyl group of residue “n” and the hydrogen atom of the amide group of the residue “n+4” on the same polypeptide chain, helps form the alpha helix

Question 6

how is the cylindrical structure formed in an alpha helix?

Answer 6

When the hydrogen bonding between these groups is repeated in a regular fashion between residues, the peptide chain twists around on itself and forms a cylindrical structure
With enough regular repetition of the hydrogen bond formation, it produces a stable alpha helix that shows the characteristic 3-point amino acids
Since R groups aren’t involved in this process, thousands of proteins within the cell can have many alpha helices

Question 7

amino acids and structure

Answer 7

Amino acids are small organic molecules with one defining property: they all possess a carboxylic acid group (-COOH) and an amino group (-NH2), both attached to a central a carbon atom

This a carbon also has a specific side chain, the identity of this is what helps us tell apart amino acids

Question 8

why is that when AA are incorporated into a polypeptide chain, the charges on the functional groups are lost

Answer 8

In the cell, where the pH is close to 7, free amino acids exist in their ionized form; but, when they are incorporated into a polypeptide chain, the charges on their NH2 and -COOH groups are lost

Question 9

describe the bonds and structure that make up proteins

Answer 9

The covalent bond b/w 2 adjacent AA in a protein chain is called a peptide bond, and the resulting chain of AA is called a polypeptide
Peptide bonds are formed by condensation rxns that link one AA to the next
The polypeptide always has as AA at one end-its N-terminus and a carboxyl group at its other end- its C-terminus
Always read starting from N-terminus
This difference in the 2 ends gives a polypeptide a definite directionality- a structural polarity

Question 10

describe the D and L forms of AA

Answer 10

Like sugars, all AA (except glycine) exist as optical isomers called D and L forms
Only L forms are ever found in proteins (although D-amino acids occur as part of bacterial cell walls and in some antibiotics, and D-serine is used as a signal molecule in the brain)

Question 11

peptide bonds

Answer 11

In proteins, AA are joined together by an amide linkage, called a peptide bond
Proteins are long polymers of AA linked by peptide bonds, and they’re written with the N-terminus toward on the left
Peptides are shorter, usually fewer than 50 AA long
The four atoms involved in each peptide bond form a rigid planar unit
There is no rotation around the C-N bond

Question 12

disulfide bond

Answer 12

A disulfide bond can form b/w 2 cysteine (CH2-S) side chains in proteins

Question 13

how enzymes promote intracellular chemical rxns

Answer 13

Enzymes promote intracellular chemical rxns by providing intricate molecular surfaces contoured with particular bumps that can cradle or exclude specific molecules

Question 14

enzyme function and example

Answer 14

Catalyze covalent bond breakage or formation

Alcohol dehydrogenase, pepsin, DNA polymerase

Question 15

structural protein function and example

Answer 15

Provide mechanical support to cells and tissues

Collagen and elastin

Question 16

transport protein function and example

Answer 16

Carry small molecules or ions

Hemoglobin (carries oxygen), transferrin (carries iron)

Question 17

motor protein function and example

Answer 17

Generate movement in cells and tissues

Myosin (provides force for humans to move), kinesin(interacts w/ microtubules to move organelles around cell)

Question 18

storage protein function and example

Answer 18

Store AA or ions
Ferritin(stores iron in liver), casein(source of AA in milk for baby mammals)

Question 19

signal protein function and example

Answer 19

Carry extracellular signals from cell to cell

Insulin(protein that controls glucose levels in the blood), netrin (attracts growing nerve cell axons to locations in developing spinal cord)

Question 20

receptor proteins function and example

Answer 20

Detect signals and transmit them to the cell’s response machinery
Rhodopsin(retina detects light), insulin receptor (allows a cell to respond to the hormone insulin by taking up glucose)

Question 21

transcription regulators function and example

Answer 21

Bind to the DNA to switch genes on or off

Lac repressor(in bacteria silences the genes for the enzymes that degrade the sugar lactose)

Question 22

special purpose protein function and example

Answer 22

Highly variable
Antifreeze proteins of Arctic fish(protects their blood against freezing), green fluorescent protein from jellyfish (emits a green light)

Question 23

how does a covalent peptide bond form?

Answer 23

A covalent peptide bond forms when the carbon atom of the carboxyl group of one AA shares electrons with the nitrogen atom from the amino group of a 2nd AA

Question 24

Because a molecule of water is eliminated, peptide bond formation is classified as a

Answer 24

condensation reaction

Question 25

polypeptide backbone structure

Answer 25

Because the 2 ends of each AA are chemically different- one end has an amino group (NH3+) and the other a carboxyl group (COO-)

Each polypeptide chain has directionality: the end carrying the amino group is called the amino terminus, or N-terminus, and the end carrying the free carboxyl group is the carboxyl terminus, or C-terminus

Projecting from the polypeptide backbone are the AA side chains- the part of the AA that’s not involved in forming peptide bonds

Side chains give each AA its unique properties

Question 26

why are long polypeptide chains very flexible

Answer 26

Long polypeptide chains are very flexible as many of the covalent bonds that link the carbon atoms in the polypeptide backbone allow free rotation of the atoms they join

Therefore proteins can fold in many different way

The shape of each folded chain is constrained by many sets of weak noncovalent bonds that form within proteins

Question 27

what are the bonds that help proteins fold and maintain their shape

Answer 27

The noncovalent bonds that help proteins fold up and maintain their shape are the hydrogen bonds, electrostatic attractions and van der Waals attractions
Because a noncovalent bond is much weaker than a covalent bond, it takes many noncovalent bonds to hold 2 regions of a polypeptide chain tightly together
The stability of each folded shape is largely determined by the combined strength of large numbers of noncovalent bonds

Question 28

hydrophobic force

Answer 28

In an aqueous environment, hydrophobic molecules, including the nonpolar side chains of particular AA, tend to be forced together to minimize their disruptive effect on the hydrogen-bonded network of the surrounding water molecules

An important factor governing the folding of any protein is the distribution of its polar and nonpolar amino acids

The nonpolar (hydrophobic) side chains tend to cluster in the interior of the folded protein

Tucked away inside the folded protein, hydrophobic side chains can avoid contact with the aq. environment that surrounds them inside a cell

Question 29

how is a conformation of a polypeptide chain determined

Answer 29

The final folded structure, or conformation, adopted by any polypeptide chain is determined by energetic considerations: a protein generally folds into the shape in which its free energy (G) is minimized
The folding process is thus energetically favourable, as it releases heat and increases the disorder of the universe

Question 30

denaturation

Answer 30

A protein can be unfolded, or denatured, by treatment with solvents that disrupt the noncovalent bonds holding the folded chain together
This converts the protein into a flexible polypeptide chain that has lost its natural shape
When the denaturing solvent is removed, and the proper conditions are provided, the protein often refolds spontaneously into its original conformation→ renaturation

Question 31

chaperone proteins

Answer 31

Protein folding in a living cell is generally assisted by a large set of special proteins called chaperone proteins
Some of these bind to partly folded chains and help them to fold along the most energetically favourable pathway

Question 32

isolation chambers

Answer 32

Others form “isolation chambers” where single polypeptide chains can fold without the risk of forming loose material in the crowded conditions of the cytoplasm
This system also requires an input of energy from ATP hydrolysis, mainly for the association and subsequent dissociation of the cap that closes off the chamber

Question 33

backbone model of a protein

Answer 33

Backbone model: shows the overall organization of the polypeptide chain and provides a straightforward way to compare the structures of related proteins

Question 34

ribbon model

Answer 34

Ribbon model: shows the polypeptide backbone in a way that emphasizes its folding patterns

Question 35

wire model

Answer 35

includes the positions of all the AA side chains
This view is useful for predicting which AA might be involved in the protein’s activity

Question 36

Space-filling model

Answer 36

Space-filling model: provides a contour map of the protein surface, which reveals which AA are exposed on the surface
Also shows how the protein might look to a small molecule such as water or to another macromolecule in cell

Question 37

alpha helix

Answer 37

a helix was the first folding pattern to be discovered and was found in the protein a-keratin

Question 38

beta sheet

Answer 38

B sheet was found in the protein fibroin, the major part of silk
Both result from hydrogen bonds that form between the N-H and C=O groups in the polypeptide backbone
Because the AA side chains aren’t involved in forming these hydrogen bonds a helices and B sheets can be generated by different AA sequences

Question 39

how is the alpha helix made?

Answer 39

The a helix is generated when a single polypeptide chain turns around itself to form a structurally rigid cylinder
A hydrogen bond is made b/w every 4th AA, linking the C=O of one peptide bond to the N-H of another
This pattern gives rise to a regular right-handed helix

Question 40

structure of polypeptide backbone

Answer 40

The polypeptide backbone, which’s hydrophilic, is hydrogen-bonded to itself inside the a helix
Here it’s shielded from the hydrophobic lipid environment of the membrane by protruding nonpolar side chains
Sometime 2 or 3 a helices will wrap around one another to form a stable structure called a coiled-coil
This structure forms when the a helices have most of their nonpolar (hydrophobic) side chains along one side so they can twist around each other with their hydrophobic side chains facing inward
This minimizes contact with the aq cytosol

Question 41

beta sheet structure (segments)

Answer 41

B sheets form rigid structures at the core of many proteins
B sheet is made when hydrogen bonds form between segments of a polypeptide chain that lie side by side
When the neighbouring segments run in the same orientation (e.g. N-terminus to C-terminus), the structure forms a parallel B sheet
When they run in opposite directions, the structure forms an antiparallel B sheet

Question 42

amyloids

Answer 42

Misfolded proteins can form amyloid structures that can cause disease
When proteins fold incorrectly, they sometimes form amyloid structures that can damage cells and even whole tissues
These amyloid structures are thought to contribute to a number of neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease

Question 43

why is the brain vulnerable to damage?

Answer 43

Because most neurons can’t regenerate, the brain is vulnerable to the damage caused by a buildup of amyloid aggregates

Question 44

prions

Answer 44

Other neurodegenerative disorders like “mad cow” disease in cattle or scrapie in sheep are caused by misfolded proteins called prions
Prions are considered infectious because the amyloid form of the protein can convert properly folded molecules of the protein into the abnormal, disease-causing conformation
These infections occur when tissues containing prions are introduced into the food chain
After being eaten, the misfolded prions can find their way to the brain, where they form aggregates that spread rapidly from cell to cell → causing the death of the affected animal or human

Question 45

primary structure

Answer 45

Because a protein’s structure begins with its AA sequence, this is considered its primary structure

Question 46

secondary structure

Answer 46

The next level of organization includes the a helices and B sheets that form within certain segments of the polypeptide chain; these folds, produced by hydrogen bonding within the polypeptide backbone, are elements of the protein’s secondary structure

Question 47

tertiary structure

Answer 47

The full 3D conformation formed by an entire polypeptide chain including the a helices, B sheets and all other loops and folds that form b/w the N- and C- termini is referred to as its tertiary structure
Heavily influenced by the many weak, noncovalent bonds that form along the polypeptide chain, b/w AA side chains and b/w side chains and the polypeptide backbone

Question 48

quaternary structure

Answer 48

If the protein molecule exists as a complex of more than one polypeptide chain, then these interacting polypeptides, held together by noncovalent bonds, form its quaternary structure

Question 49

protein domain

Answer 49

This organizational unit is the protein domain, which is defined as any segment of a polypeptide chain that can fold independently into a compact, stable structure

Question 50

how can an extended protein filament be produced

Answer 50

A chain of identical protein molecules can be formed if the binding site on one protein molecule is complementary to another region on the surface of another protein molecule of the same type

Because each protein molecule is bound to its neighbour in an identical way, the molecules will often be arranged in a helix that can be extended indefinitely in either direction

This can produce an extended protein filament

Question 51

globular proteins

Answer 51

where the polypeptide chain folds up into a compact shape like a ball with an irregular surface
E.g. enzymes

Question 52

fibrous proteins

Answer 52

Fibrous proteins→ these proteins are elongated with a rod like shape such as collagen or a keratin filament

Question 53

coiled coil formation

Answer 53

An a-keratin molecule is a dimer of 2 identical subunits, with the long a helices of each subunit forming a coiled-coil
These coiled-coil regions are capped at either end by globular domains containing binding sites that allow them to assemble into ropelike intermediate filaments
This is a component of the cytoskeleton that gives cells mechanical strength

Question 54

covalent cross-linkages

Answer 54

Extracellular proteins are often stabilized by covalent cross-linkages
To help maintain the structures of some proteins, the polypeptide chains are often stabilized by covalent cross-linkages
These can tie together 2 AA in the same polypeptide chain or join together many polypeptide chains in a large protein complex
The most common cross linkages in proteins are sulfur-sulfur bonds
These disulfide bonds are used to reinforce a secreted protein’s structure or to join 2 different proteins together
They don’t change a protein’s conformation, but instead act as a sort of “atomic staple” to reinforced the protein’s most favoured conformation

Question 55

How can the changes in shape experienced by proteins be used to generate such orderly movements?

Answer 55

A protein that’s required to walk along a cytoskeletal fiber can move by undergoing a series of conformational changes

However, with nothing to drive these changes in one direction or the other, the shape changes will be reversible and the protein will wander randomly

To force the protein to move in one direction, the conformational changes must be unidirectional
-To achieve this, one of the steps must be made irreversible
-E.g. by coupling one of the conformational changes to the hydrolysis of an ATP molecule that’s tightly bound to the protein

Question 56

scaffold proteins

Answer 56

Many interacting proteins are brought together by scaffolds
Many protein complexes are brought together by scaffold proteins, large molecules that contain binding sites recognized by multiple proteins
By binding a specific set of interacting proteins, a scaffold can greatly enhance the rate of a chemical rxn or cell process
These proteins cluster under the plasma membranes of communicating nerve cells, allowing them both to transmit and to respond to the appropriate messages when stimulated to do so

Question 57

biomolecular condensate

Answer 57

Biomolecular condensate→ a large aggregate of phase-separated macromolecules that creates a region with a special biochemistry without the use of an encapsulating membrane
Each condensate contains at least one type of scaffold protein or scaffold RNA molecule that can interact with other molecules called clients, which become concentrated there

Question 58

phase interaction

Answer 58

Phase interaction → a property where a network of weak interactions allows individuals allows individual molecules to come and go, while the condensate as a whole remains intact and separated from its surroundings

Question 59

chromatography

Answer 59

To isolate the desired protein, the standard approach involves purifying the protein through a series of chromatography steps, which use different materials to separate the individual components of a complex mixture into portions
The most efficient forms of protein chromatography separate polypeptides on the basis of their ability to bind to a particular molecule, a process called affinity chromatography

Question 60

electrophoresis

Answer 60

Proteins can also be separated by electrophoresis
In this technique, a mixture of proteins is loaded onto a polymer gel and subjected to an electric field

Question 61

mass spectrometry

Answer 61

A faster way to determine the AA sequence of proteins that have been isolated from organisms for which the full genome sequence is known is a method called mass spectrometry
Sensitive technique that enables the determination of the exact mass of each of the molecules in a complex mixture