4.1 Molecular Structure of Proteins

Question 1

What determines the protein’s shape and function?

Answer 1

the exact order of amino acids

Question 2

How are R groups grouped?

Answer 2

according to their properties, with a particular emphasis on whether they are hydrophobic, hydrophilic, or have special characteristics that might affect a protein’s structure

these properties strongly influence how a polypeptide folds, and affect the 3D shape of the protein

Question 3

Why do hydrophobic amino acids not readily interact with water or form hydrogen bonds?

Answer 3

• most hydrophobic amino acids have nonpolar R groups composed of hydrocarbon chains or uncharged carbon rings
• because water molecules in the cell form hydrogen bonds with each other instead of with hydrophobic R groups, the hydrophobic R groups tend to aggregate each other
• aggregations is stabilized by weak van der Waals forces in which asymmetries in electron distribution create temporary charges in the interacting molecules, which are then attracted to each other
• tendency of hydrophilic water molecules to interact with each other and for hydrophobic molecules to interact with each other is the very same tendency that leads to the formation of oil droplets in water
• also the reason why most hydrophobic amino acids tend to be buried in the interior of folded proteins, where they do not interact with water

Question 4

Which amino acids have a permanent charge separation?

Answer 4

ones with polar R groups

Question 5

What is a permanent charge separation?

Answer 5

one end of the R group is slightly more negatively charged than the other

(polar molecules are hydrophilic and they tend to form H-bonds with each other or with water molecules)

Question 6

Describe the R groups of basic and acidic amino acids.

Answer 6

• typically charged, and therefore strongly polar
• at the pH of a cell, R groups of BASIC amino acids gain a proton and become negatively charged, while R groups of acidic amino acids LOSE a proton and become positively charged
• because the R groups of these are charged, they are usually located on the outside surface of the folded molecule
• charged groups can form ionic bonds with each other and with other charged molecules in the environment, with a negatively charged group or molecule bonding with a positively charged group or molecule
• this ability to bind another molecule or opposite charge is an important way in which proteins can associate with each other or with other macromolecules such as DNA

Question 7

How is glycine different from other amino acids?

Answer 7

• symmetrical: R group is hydrogen, exactly like the hydrogen on the other side of the alpha carbon
  (all other AA have 4 different groups attached to alpha carbon and are ASYMMETRIC)
• nonpolar and small enough to tuck into spaced where other R groups would not fit, which allows for freer rotation around C-N bond since its R group does not get in the way of the R groups of neighbouring amino acids
• increases flexibility of the polypeptide backbone, which can be important in the folding of the protein

Question 8

How is proline different from other amino acids?

Answer 8

• R group is linked back to the amino group, which creates a kink or bend in the polypeptide chain and restricts rotation of the C-N bond, thereby imposing constraints on protein folding in its vicinity
• opposite effect of glycine

Question 9

How is cysteine different from other amino acids?

Answer 9

• makes a special contribution to protein folding through its
  —SH group
• when two cysteine side chains in the same or different polypeptides come into proximity, they can react to form an S—S disulfide bond, which covalently joins the side chains
• these bonds are stronger than the ionic interactions of other pairs of amino acid, and form cross-bridges that can connect different parts of the same protein or even different proteins
• this property contributes to the overall structure of single proteins or combinations of proteins

Question 10

What is a peptide bond?

Answer 10

covalent bond that links the carbon atom in the carboxyl group of one amino acid to the nitrogen atom in the amino group of another amino acid

Question 11

Why are the electrons of the peptide bond more attached to the C=O group than to the NH group?

Answer 11

because of the electronegativity of the oxygen atom

the peptide bond has some of the characteristics of the double bond, is shorter than a single bond, and is not free to rotate like a single bond around their central axes

Question 12

What is a protein?

Answer 12

synonym for polypeptide, especially when the polypeptide chain has folded into a stable, 3D conformation

Question 13

What are amino acid residues?

Answer 13

amino acids that are incorporated into a protein

Question 14

Describe the amino and carboxyl ends of a polypeptide chain at physiological pH.

Answer 14

in their chared states

amino: NH3+
carboxyl: COO-

however for simplicity, we call them NH2 and COOH

Question 15

What is the primary structure?

Answer 15

sequence of amino acids in a protein

Question 16

What does the sequence of amino acids determine?

Answer 16

how the protein folds

Question 17

What is the secondary structure?

Answer 17

structure formed by interactions between stretches of amino acids in a protein

Question 18

What is the tertiary structure?

Answer 18

overall 3D shape of a protein, formed by interactions between secondary structures

Question 19

What is the quaternary structure?

Answer 19

structure that results from the interactions of several polypeptide chains

Question 20

What happens when proteins are fully folded?

Answer 20

• some proteins contain pockets with positively or negatively charged side chains at just the right positions to trap small molecules
• some have surfaces that can bind another protein or a sequence of nucleotides in DNA or RNA
• some form rigid rods for structural support
• some still keep their hydrophobic side chains away from water molecules by inserting into the cell membrane

Question 21

What is a major contributor to the secondary structure?

Answer 21

hydrogen bonds can form between the carbonyl group in on peptide bond and the amide group in another, allowing localized regions of the polypeptide chain to fold

Question 22

What are the two different secondary structures?

Answer 22

alpha helix and beta sheet

Question 23

Describe the alpha helix.

Answer 23

• polypeptide backbone twister tightly in a right-handed coil with 3.6 amino acids per complete turn
• stabilized by hydrogen bonds that form between each amino acid’s carbonyl group (C=O) and the amide group (N-H) four residues ahead in the sequence
• R groups project outward
• chemical properties of the projecting R groups largely determine where the alpha helix is positioned in the folded protein and how it might interact with other molecules

Question 24

Describe the beta sheet.

Answer 24

• polypeptide folds back and forth on itself, forming a pleated sheet that is stabilized by hydrogen bonds between carbonyl groups in one chain and amide groups in the other chain across the way
• R groups project alternately above and below the plane of the sheet
• 4-10 polypeptide chains aligned side by side, with the amide groups in each chain hydrogen-bonded to the carbonyl groups on either side

Question 25

How can beta sheets be formed?

Answer 25

• polypeptide chains are antiparallel (opposite directions) which is more stable because the carbonyl and amide groups are more favourably aligned for hydrogen bonding
• can also be formed by hydrogen bonds between polypeptide chains that are parallel (same direction)

Question 26

What is the tertiary structure defined by?

Answer 26

by interactions between amino acid R groups

Question 27

What does the secondary structure rely on?

Answer 27

interactions in the polypeptide backbone and is relatively independent of R groups

Question 28

How is tertiary structure determined?

Answer 28

by the spatial distribution of hydrophilic and hydrophobic R groups along the molecule, as well as many different types of chemical bonds and interactions (ie. ionic, hydrogen, van der Waals) that form between various R groups

Question 29

What do tertiary structures usually include in their backbone?

Answer 29

amino acids whose R groups formed bonds with each other may be far apart in the polypeptide chain, but can end up near each other in the folded protein

loops or turns in the backbone that allow these R groups to sit near each other in space and for bonds to form

Question 30

Why does tertiary structure determine function?

Answer 30

because it is the 3D shape of the molecule (contours and distribution of charges on the outside of the molecule and the presence of pockets that might bind with smaller molecules on the inside) that enables the protein to serve as structural support, membrane channel, enzyme, or signalling molecule

Question 31

What does denatured mean?

Answer 31

unfolding of proteins by chemical treatment or high temperature that disrupts the hydrogen and ionic bonds golding the tertiary structure together

proteins lose their functional activity

Question 32

Describe a protein with quaternary structure.

Answer 32

• polypeptide subunits may be either identical or different
• subunits can influence each other in subtle ways and influence their function

(ie. hemoglobin in RBC that carries oxygen has four subunits. when one of these subunits binds to oxygen, a slight change in its structure is transmitted to the other subunits, making it easier for them to take up oxygen. in this way, oxygen transport from the lungs to the tissues is improved)

Question 33

For ~75% of proteins, how long is the folding process?

Answer 33

within milliseconds

Question 34

Some proteins fold more slowly. Why is it dangerous?

Answer 34

the longer these polypeptides remain in a denatured (unfolded) state, the longer their hydrophobic groups are exposed to other macromolecules in the crowded cytoplasm

hydrophobic effect, along with van der Waals interactions, tends to bring the exposed hydrophobic groups together, and their inappropriate aggregation may prevent proper folding

Question 35

Why can correctly doled proteins sometimes unfold?

Answer 35

because of elevated temperature, and in the denatured state they are subject to the same risks of aggregation

Question 36

What are chaperones?

Answer 36

proteins evolved by cells that help protect slow-folding or denatured proteins until they can attain their proper 3D

Question 37

What do chaperones bind with?

Answer 37

bind with hydrophobic groups and nonpolar R groups to shield them from inappropriate aggregation, and in repeated cycles of binding and release they give the polypeptide time to find its correct shape