Tertiary Structure (Proteins)

Question 1

What defines the tertiary structure of a protein?

Answer 1

The overall 3D spatial arrangement of atoms in a polypeptide chain

Question 2

What percentage of a typical polypeptide chain exhibits secondary structure in its tertiary form?

Answer 2

Approximately 70%

Question 3

What are protein motifs?

Answer 3

Specific combinations of secondary structural elements that recur in protein tertiary structure

Question 4

What is a protein domain?

Answer 4

A compact, functionally distinct region of a protein, often containing several motifs

Question 5

Which interactions stabilize the tertiary structure of proteins?

Answer 5

Van der Waals forces, hydrogen bonds, hydrophobic interactions, ionic bonds, and sometimes covalent disulfide bonds

Question 6

What is the approximate energy range of van der Waals interactions in proteins?

Answer 6

0.4 – 4 kJ/mol

Question 7

What is the typical energy range for hydrogen bonds in protein structure?

Answer 7

12 – 30 kJ/mol

Question 8

How do hydrophobic interactions contribute to protein structure?

Answer 8

By driving nonpolar side chains into the protein core to avoid water

Question 9

Why are hydrophobic residues sometimes exposed in membrane proteins?

Answer 9

To interact with the lipid bilayer of the membrane

Question 10

What are prosthetic groups in proteins?

Answer 10

Covalently attached cofactors essential for protein function

Question 11

What is a holoprotein?

Answer 11

A functional protein consisting of an apoprotein and its prosthetic group

Question 12

Why does myoglobin serve as a model for tertiary structure?

Answer 12

Because it is a small, well-characterized monomeric protein with a known function and a clearly defined globular domain

Question 13

How many α-helices are found in myoglobin?

Answer 13

Eight

Question 14

What is the function of the heme group in myoglobin?

Answer 14

To reversibly bind oxygen via its iron (Fe) ion

Question 15

How does myoglobin prevent Fe²⁺ oxidation?

Answer 15

By embedding the heme in a hydrophobic pocket; hydrophobic amino acids prevent Fe²⁺ oxidation

Question 16

Which amino acid in myoglobin stabilizes oxygen binding?

Answer 16

Histidine

Question 17

How does myoglobin reduce CO binding to heme?

Answer 17

The globin structure alters the binding site geometry, reducing CO’s affinity relative to O₂

Question 18

Define protein denaturation.

Answer 18

The loss of tertiary structure and biological function due to disruption of stabilizing interactions

Question 19

What are chaotropic agents?

Answer 19

Chemicals like urea or guanidinium hydrochloride that disrupt H-bonds and weaken hydrophobic interactions

Question 20

What is the melting temperature (Tm) of a protein?

Answer 20

The temperature at which half the protein population becomes denatured

Question 21

What are pK₁, pK₂, and pK_R in a protein?

Answer 21

pK₁ and pK₂ are the pKa values for the C- and N-termini; pK_R corresponds to the ionizable side chains

Question 22

How does pH affect protein folding?

Answer 22

By altering the ionization state of charged residues, which affects hydrogen and ionic bonds

Question 23

What does the isoelectric point (pI) represent?

Answer 23

The 𝐩𝐇 at which a protein carries no net charge

Question 24

What experiment demonstrated that tertiary structure is determined by primary structure?

Answer 24

Anfinsen’s ribonuclease refolding experiment

Question 25

What were the denaturants used in the Anfinsen experiment?

Answer 25

Urea and 2-mercaptoethanol

Question 26

What conclusion did Anfinsen’s experiment support?

Answer 26

That protein folding is reversible and directed by the amino acid sequence

Question 27

Why is protein denaturation often irreversible in vivo?

Answer 27

Because unfolded proteins can aggregate and form insoluble amyloids

Question 28

What is Levinthal’s paradox?

Answer 28

It shows that random folding of proteins would take longer than the age of the universe, implying specific folding pathways

Question 29

What is meant by hydrophobic collapse in protein folding?

Answer 29

The initial compaction of a protein due to burial of hydrophobic residues, facilitating further folding

Question 30

What are molecular chaperones?

Answer 30

Proteins that assist the proper folding of other proteins in vivo

Question 31

Name two molecular chaperones involved in protein folding.

Answer 31

Hsp70 and Hsp40

Question 32

What are chaperonins?

Answer 32

Large protein complexes (e.g., GroEL-GroES) that provide a chamber for correct folding

Question 33

What is proteostasis?

Answer 33

The homeostasis of protein synthesis, folding, and degradation in a cell

Question 34

What factors challenge proteostasis?

Answer 34

pH changes, temperature fluctuations, oxidative stress, high protein concentrations, and mutations

Question 35

What neurodegenerative diseases are linked to protein misfolding?

Answer 35

Alzheimer’s, Parkinson’s, and prion diseases

Question 36

How do amyloids relate to protein structure?

Answer 36

They are insoluble fibrillar aggregates formed from misfolded proteins

Question 37

How does protein misfolding lead to disease?

Answer 37

By 𝐝𝐢𝐬𝐫𝐮𝐩𝐭𝐢𝐧𝐠 cellular function and triggering 𝐜𝐞𝐥𝐥 𝐝𝐞𝐚𝐭𝐡 via 𝐭𝐨𝐱𝐢𝐜 𝐚𝐠𝐠𝐫𝐞𝐠𝐚𝐭𝐞𝐬

Question 38

How does temperature affect protein tertiary structure?

Answer 38

By disrupting weak interactions like hydrogen and van der Waals bonds

Question 39

Why is structure prediction important in protein science?

Answer 39

It helps to understand function, design drugs, and study disease mechanisms

Question 40

Which technique is traditionally used to determine protein 3D structure?

Answer 40

X-ray crystallography

Question 41

What recent advance has transformed protein structure prediction?

Answer 41

AI-based models like AlphaFold

Question 42

Why is myoglobin colored?

Answer 42

Because its heme group absorbs UV-visible light, giving it a red color

Question 43

What causes the UV-visible absorbance of the heme group?

Answer 43

Electron resonance within the porphyrin ring and iron ion

Question 44

Why is protein folding considered thermodynamically favorable?

Answer 44

Because the native folded state is the lowest-energy conformation

Question 45

What structural feature ensures solubility in globular proteins?

Answer 45

Hydrophilic residues on the surface and hydrophobic ones buried inside

Question 46

What does a high Tm indicate about a protein’s stability?

Answer 46

That the protein is thermally stable and resists denaturation

Question 47

Why are histidines often involved in active sites?

Answer 47

Due to their ability to act as proton donors or acceptors near physiological pH

Question 48

What determines the specificity of prosthetic group binding in proteins?

Answer 48

The 3D arrangement of surrounding amino acids creating a binding pocket

Question 49

What are the challenges to proteostasis?

Answer 49

- 𝗦𝘁𝗿𝗲𝘀𝘀 𝗰𝗮𝘂𝘀𝗶𝗻𝗴 𝗮𝗴𝗲𝗻𝘁𝘀: changes in pH, T, oxidative stress - 𝗣𝗵𝘆𝘀𝗶𝗼𝗹𝗼𝗴𝗶𝗰𝗮𝗹 𝗽𝗿𝗼𝗰𝗲𝘀𝘀𝗲𝘀: protein synthesis - 𝗣𝗿𝗼𝘁𝗲𝗶𝗻 𝗰𝗼𝗻𝗰𝗲𝗻𝘁𝗿𝗮𝘁𝗶𝗼𝗻: unfolded proteins put other proteins at risk - 𝗨𝗻𝘀𝘁𝗮𝗯𝗹𝗲 𝗽𝗿𝗼𝘁𝗲𝗶𝗻𝘀 (10%) - 𝗠𝘂𝘁𝗮𝘁𝗶𝗼𝗻𝘀

Question 50

What is an apoprotein?

Answer 50

A protein missing an essential part

Question 51

What are conjugated proteins?

Answer 51

Those that present 𝗮𝗻𝗼𝘁𝗵𝗲𝗿 molecule in their structure that is 𝗻𝗼𝘁 a protein