3. Proteins

Question 1

Describe some functions proteins carry out aside from being ‘the building blocks of the cell’

Answer 1

Proteins that are enzymes provide the intricate molecular surfaces inside a cell that catalyse its many chemical reactions.

Proteins embedded in the plasma membrane form channels and pumps that control the passage of small molecules into and out of the cell.

Other proteins carry messages from one cell to another, or act as signal integrators that relay sets of signals inward from the plasma membrane to the cell nucleus.

Yet others serve as tiny molecular machines with moving parts. Other specialized proteins act as antibodies, toxins, hormones, antifreeze molecules, elastic fibers, ropes, or sources of luminescence.

Question 2

Give two examples of proteins which serve as tiny molecular machines with moving parts

Answer 2

Kinesin, for example, propels organelles through the cytoplasm; topoisomerase can untangle knotted DNA molecules.

Question 3

What is significant about proteins from a chemical point of view?

Answer 3

From a chemical point of view, proteins are by far the most structurally complex and functionally sophisticated molecules known.

Question 4

How many amino acids are coded for in an organisms DNA?

Answer 4

There are 20 different of amino acids in proteins that are coded for directly in an organism’s DNA, each with different chemical properties.

Question 5

How do these amino acids relate to proteins?

Answer 5

A protein molecule is made from a long unbranched chain of these amino acids, each linked to its neighbour through a covalent peptide bond. Proteins are therefore also known as polypeptides.

Question 6

What is meant by a polypeptide backbone?

Answer 6

The repeating sequence of atoms along the core of the polypeptide chain is referred to as the polypeptide backbone. Attached to this repetitive chain are those portions of the amino acids that are not involved in making a peptide bond and that give each amino acid its unique properties: the 20 different amino acid side chains

Question 7

What are some of the main differential characteristic these side chains may have?

Answer 7

Some of these side chains are nonpolar and hydrophobic (“water-fearing”), others are negatively or positively charged, some readily form covalent bonds, and so on.

Question 8

Name the amino acids with non-polar sidechains, also give their symbols

Answer 8

Alanine Ala A
Glycine Gly G
Valine Val V
Leucine Leu L
Isoleucine Ile I
Proline Pro P
Phenylalanine Phe F
Methionine Met M
Tryptophan Trp W
Cysteine Cys C

Question 9

Name the amino acids with negatively charged polar side chains, also give their symbols

Answer 9

Aspartic acid Asp D
Glutamic acid Glu E

Question 10

Name the amino acids with positively charged polar side chains, also give their symbols

Answer 10

Arginine Arg R
Lysine Lys K
Histidine His H

Question 11

Name the amino acids with uncharged polar side chains, also give their symbols

Answer 11

Asparagine Asn N
Glutamine Gln Q
Serine Ser S
Threonine Thr T
Tyrosine Tyr Y

Question 12

What aspect of atoms apply constraints to the molecules created by proteins?

Answer 12

Atoms behave almost as if they were hard spheres with a definite radius (their van der Waals radius). The requirement that no two atoms overlap plus other constraints limit the possible bond angles in a poly-peptide chain, severely restricting the possible three-dimensional arrangements (or conformations) of atoms.

Question 13

What is the folding of a protein also determined by?

Answer 13

The folding of a protein chain is also determined by many different sets of weak noncovalent bonds that form between one part of the chain and another.

Question 14

Do these non-covalent bonds within the chain form between the polypeptide backbone or the side chains?

Answer 14

These involve atoms in the polypeptide backbone, as well as atoms in the amino acid side chains

Question 15

What are the three types of weak non-covalent bonds involved in this?

Answer 15

There are three types of these weak bonds: hydrogen bonds, electrostatic attractions, and van der Waals attractions

Question 16

What fourth weak force also has a central role in determining the shape of a protein?

Answer 16

hydrophobic clustering force— hydrophobic molecules, including the nonpolar side chains of particular amino acids, tend to be forced together in an aqueous environment in order to minimise their disruptive effect on the hydrogen-bonded network of water molecules

Question 17

How does the hydrophobic clustering force play a role in the folding of proteins?

Answer 17

An important factor governing the folding of any protein is the distribution of its polar and nonpolar amino acids. The nonpolar (hydropho-
bic) side chains in a protein—belonging to such amino acids as phenylalanine, leucine, valine, and tryptophan—tend to cluster in the interior of the molecule (just as hydrophobic oil droplets coalesce in water to form one large droplet).

This enables them to avoid contact with the water that surrounds them inside a cell. In contrast, polar groups—such as those belonging to arginine, glutamine, and histidine—tend to arrange themselves near the outside of the molecule, where they can form hydrogen bonds with water and with other polar molecules

Question 18

When are polar amino acids typically buried inside a protein?

Answer 18

Polar amino acids buried within the protein are usually hydrogen-bonded to other polar amino acids or to the polypeptide backbone.

Question 19

How does the conformation of a protein relate to a key topic of chapter 2?

Answer 19

The final folded structure, or conformation, of any polypeptide chain is generally the one that minimises its free energy.

Question 20

Biologists have studied protein folding in a test tube using highly purified proteins. What have they observed through treatments with certain solvents?

Answer 20

Treatment with certain solvents, which disrupt the noncovalent interactions holding the folded chain together, unfolds, or denatures, a protein. This treatment converts the protein into a flexible polypeptide chain that has lost its natural shape.

When the denaturing solvent is removed, the protein often refolds spontaneously, or renatures, into its original conformation.

Question 21

What does this denature and renature studies suggest?

Answer 21

This indicates that the amino acid sequence contains all of the information needed for specifying the three-dimensional shape of a protein, a critical point for understanding cell biology.

Question 22

Do most proteins have a single stable conformation?

Answer 22

Most proteins fold up into a single stable conformation. However, this confor- mation changes slightly when the protein interacts with other molecules in the cell. This change in shape is often crucial to the function of the protein, as we see later.

Question 23

How may a protein be assisted in its folding?

Answer 23

Although a protein chain can fold into its correct conformation without out- side help, in a living cell special proteins called molecular chaperones often assist in protein folding. Molecular chaperones bind to partly folded polypeptide chains and help them progress along the most energetically favourable folding pathway.

Question 24

What is required of the chaperones in the crowded conditions of the cytoplasm?

Answer 24

Chaperones are required to prevent the temporarily exposed hydrophobic regions in newly synthesised protein chains from associating with each other to form protein aggregate

Question 25

How long are proteins typically?

Answer 25

Proteins come in a wide variety of shapes, and most are between 50 and 2000 amino acids long.

Question 26

What subdivisions exist in many proteins?

Answer 26

Large proteins usually consist of several distinct protein domains—structural units that fold more or less independently of each other

Question 27

Name four ways in which the structure of a protein may be displayed

Answer 27

(A) a polypeptide backbone model,
(B) a ribbon model,
(C) a wire model that includes the amino acid side chains, and
(D) a space- filling model

Question 28

When we compare the three-dimensional structures of many different protein molecules, what is clear about the patterns in conformation?

Answer 28

Although the overall conformation of each protein is unique, two regular folding patterns are often found within them.

Question 29

What are these two patterns called and how were they first found?

Answer 29

Both patterns were discovered more than 60 years ago from studies of hair and silk. The first folding pattern to be discovered, called the α helix, was found in the protein α-keratin, which is abundant in skin and its derivatives—such as hair, nails, and horns. Within a year of the discovery of the α helix, a second folded structure, called a β sheet, was found in the protein fibroin, the major constituent of silk.

Question 30

Why are these two patterns particularly common?

Answer 30

These two patterns are particularly common because they result from hydrogen-bonding between the N–H and C=O groups in the polypeptide backbone, without involving the side chains of the amino acids. Thus, although incompatible with some amino acid side chains, many different amino acid sequences can form them.

Question 31

What do the cores of many proteins contain?

Answer 31

The cores of many proteins contain extensive regions of β sheet.

Question 32

How may B-sheets form?

Answer 32

β sheets can form either from neighbouring segments of the polypeptide backbone that run in the same orientation (parallel chains) or from a polypeptide backbone that folds back and forth upon itself, with each section of the chain running in the direction opposite to that of its immediate neighbours (antiparallel chains).

Question 33

Which type of B-sheet could be described as ‘rigid’?

Answer 33

Both types of β sheet produce a very rigid structure, held together by hydrogen bonds that connect the peptide bonds in neighbouring chains

Question 34

When is an a-helix formed?

Answer 34

An α helix is generated when a single polypeptide chain twists around on itself to form a rigid cylinder.

Question 35

What bonds hold an a helix?

Answer 35

A hydrogen bond forms between every fourth peptide bond, linking the C=O of one peptide bond to the N–H of another

Question 36

Describe the regular unit which this gives rise to

Answer 36

This gives rise to a regular helix with a complete turn every 3.6 amino acids.

Question 37

Describe whether there are any a helices or B sheets present in an aforementioned protein domain

Answer 37

This gives rise to a regular helix with a complete turn every 3.6 amino acids. The SH2 protein domain contains two α helices, as well as a three-stranded antiparallel β sheet.

Question 38

What proteins are particularly abundant in a helices?

Answer 38

Regions of α helix are abundant in proteins located in cell membranes, such as transport proteins and receptors.

Question 39

What are the portions of transmembrane proteins that cross the bilipid layer typically composed of?

Answer 39

Portions of a transmembrane protein that cross the lipid bilayer usually cross as α helices composed largely of amino acids with nonpolar side chains. The polypeptide backbone, which is hydrophilic, is hydrogen-bonded to itself in the α helix and shielded from the hydrophobic lipid environment of the membrane by its pro- truding nonpolar side chains

Question 40

Describe a common structure made up of a helices

Answer 40

In other proteins, α helices wrap around each other to form a particularly sta- ble structure, known as a coiled-coil. This structure can form when the two (or in some cases, three or four) α helices have most of their nonpolar (hydrophobic) side chains on one side, so that they can twist around each other with these side chains facing inward

Question 41

What function do coiled coil structure typically carry out?

Answer 41

Long rodlike coiled-coils provide the structural framework for many elongated proteins. Examples are α-keratin, which forms the intracellular fibers that reinforce the outer layer of the skin and its appendages, and the myosin molecules responsible for muscle contraction.

Question 42

What levels of organisation in the structure of a protein to scientists distinguish?

Answer 42

The amino acid sequence is known as the primary structure. Stretches of polypeptide chain that form α helices and β sheets constitute the protein’s secondary structure. The full three-dimensional organisation of a polypeptide chain is sometimes referred to as the tertiary structure, and if a particular protein molecule is formed as a complex of more than one polypeptide chain, the complete structure is designated as the quaternary structure.

Question 43

Studies of the conformation, function, and evolution of proteins have also revealed the central importance of a unit of organisation distinct from these four. What unit is this?

Answer 43

This is the protein domain, a substructure produced by any contiguous part of a polypeptide chain that can fold independently of the rest of the protein into a compact, stable structure.

Question 44

How long are domains typically?

Answer 44

A domain usually contains between 40 and 350 amino acids, and it is the modular unit from which many larger proteins are constructed

Question 45

What are different domains of a protein often associated with?

Answer 45

The different domains of a protein are often associated with different functions