Membraan architectuur 2

Question 1

In which membrane do β-barrels, forming a pore, occur?

A. Inner mitochondrial membrane
B. Endoplasmic reticulum membrane
C. E. coli outer membrane
D. Golgi membrane

Answer 1

C

Question 2

Propose potential applications of the information gained from studying membrane proteins in drug development.

Answer 2

The insights gained from studying membrane proteins have profound implications for drug development. Membrane proteins, including receptors, channels, and transporters, play crucial roles in various physiological processes. Understanding their structures, functions, and interactions with membranes provides a foundation for targeted drug design. Potential applications include the development of drugs that modulate specific membrane protein activities, leading to therapeutic interventions in conditions such as neurological disorders, cardiovascular diseases, and cancer. Moreover, knowledge of membrane properties can guide the design of drug delivery systems, ensuring efficient transport across cell membranes. The study of membrane proteins is instrumental in advancing precision medicine by allowing the development of drugs tailored to specific cellular and molecular targets.

Question 3

How does the thickness of the membrane affect the localization of proteins?

Answer 3

The thickness of the membrane influences the localization of proteins by affecting their hydrophobic matching. Proteins with transmembrane segments must have a length that matches the thickness of the membrane to maintain stability. If a protein’s hydrophobic segment is too short or too long for the membrane thickness, it may lead to unfavorable hydrophobic mismatch, impacting the protein’s localization. Adjusting the length of transmembrane segments allows proteins to reside in specific membrane compartments.

Question 4

The hydrophobic thickness of a membrane influences the ______________ of membrane proteins.

Answer 4

Localization

Question 5

Choose the correct statements regarding membrane proteins:
A. α-helix bundles are the most common structure in all types of membranes.
B. β-barrels are exclusive to the outer membrane of E. coli.
C. More than 50% of all drugs target membrane proteins.
D. The hydrophobic thickness of the plasma membrane is smaller than that of the Golgi membrane.

Answer 5

A-F, B-T, C-T, D-F

Question 6

Briefly explain the relationship between the Meyer‐Overton rule and anesthetics.

Answer 6

The Meyer‐Overton rule correlates the potency of anesthetics with their lipid solubility. According to this rule, the higher the lipid solubility of an anesthetic, the more potent it is. The rule suggests that anesthetics act by dissolving in the lipid bilayer of cell membranes, altering their properties. The “aquarium” experiment with kikkervisjes and liposomes supports the idea that anesthetics interact with membranes, influencing their fluidity and potentially leading to changes in the activity of membrane proteins, including ion channels.

Question 7

What are the two types of secondary structures mentioned for integral membrane proteins?

a. β-turn and coil
b. α-helix and β-barrel
c. γ-sheet and loop
d. δ-helix and spiral

Answer 7

B

Question 8

Consider the challenges and ethical considerations associated with studying amyloids for medical applications.

Answer 8

Studying amyloids for medical applications presents challenges, including the complexity of the aggregation process, potential toxicity of intermediate species, and difficulty in targeting specific forms of amyloids. Ethical considerations include the use of animal models, informed consent in clinical trials, and balancing potential benefits with risks. Additionally, ensuring that research aligns with ethical standards and prioritizing patient well-being are crucial aspects of amyloid-related studies.

Question 9

Describe the process of reconstitution in the context of membrane proteins.

Answer 9

Reconstitution involves integrating purified membrane proteins into artificial lipid bilayers, creating a system that mimics a natural membrane environment. Detergents are initially used to solubilize the proteins from their native membranes. The detergent-protein complex is then mixed with lipids, and through methods like dialysis or detergent removal, the detergent is gradually replaced with lipids, leading to the spontaneous formation of proteoliposomes or supported lipid bilayers. This process allows researchers to study membrane proteins in controlled environments.

Question 10

What is the significance of the lag phase in the fibril formation of IAPP?

Answer 10

The lag phase in the fibril formation of IAPP is a critical period during which nucleation events occur. It represents the time required for the formation of stable aggregates, and the length of the lag phase is influenced by factors such as protein concentration. Understanding the lag phase is essential for studying the kinetics of fibril formation and may provide insights into potential interventions or inhibitors that could modulate this process, with implications for diseases associated with amyloid formation.

Question 11

Match the following terms with their descriptions:

A. Fibril Formation
B. Hydrophobic Matching
C. Lipid “Packing”
D. Helical Wheel
_______________ - Visualization of amphipathic helix polarity.
_______________ - Formation of amyloid structures.
_______________ - Adjustment of membrane protein length to membrane thickness.
_______________ - Influence of lipids on lateral pressure profile.

Answer 11

D-A-B-C

Question 12

______________ is a method to determine if a helix is amphilpathic based on amino acid sequence.

Answer 12

Helical wheel

Question 13

What is the Meyer‐Overton rule related to?

a. Protein folding
b. Membrane permeability
c. Enzyme activity
d. DNA replication

Answer 13

B

Question 14

Discuss the potential implications of hydrophobic mismatch in the context of membrane protein structure and function.

Answer 14

Hydrophobic mismatch occurs when the length of a transmembrane segment in a protein does not match the thickness of the lipid bilayer. This mismatch can have significant implications for the stability and function of membrane proteins. Proteins may undergo conformational changes, aggregate, or adjust their length to accommodate the membrane. Hydrophobic mismatch is critical in determining the proper localization of proteins and understanding how cells regulate membrane protein structure to maintain optimal functionality.

Question 15

How many hydrophobic amino acids are approximately needed to span a membrane?

a. 10
b. 15
c. 20
d. 25

Answer 15

C

Question 16

In the Meyer‐Overton rule, the y-axis represents the ______________ of anesthetics.

Answer 16

Potency

Biologische werking van een medicijn

Question 17

Explain the role of hydrophobic amino acids in determining whether a protein is likely a transmembrane protein.

Answer 17

Hydrophobic amino acids are crucial for the integration of proteins into membranes. In transmembrane proteins, these amino acids form hydrophobic regions, such as α-helices or β-sheets, allowing the protein to span the hydrophobic core of the lipid bilayer. The presence of approximately 20 consecutive hydrophobic amino acids is often a characteristic feature of transmembrane domains, facilitating the protein’s stable insertion into the lipid environment.

Question 18

What is the primary function of DesK, the bacterial thermosensor?

A. Ion transport
B. Temperature sensing
C. Glucose metabolism
D. Oxygen transport

Answer 18

B

Question 19

Match the secondary structure with its characteristics:
A. α-helix

B. β-sheet

• 3.6 residues per turn, right-handed
• Hydrogen bonds between NH groups of adjacent chains
• Forms a barrel structure in membranes

Question 20

What is the typical length per amino acid along the helix axis in an α-helix?

A. 2 Å
B. 1.5 Å
C. 3 Å
D. 5 Å

Answer 20

B

Question 21

In which type of membrane do β-barrel proteins occur?

a. Plasma membrane
b. Golgi membrane
c. E. coli outer membrane
d. Mitochondrial membrane

Answer 21

C

Question 22

True/False:
A single α-helix can form a pore in a membrane.

Answer 22

False

Question 23

Membrane proteins often have approximately __ hydrophobic amino acids in a row, spanning about __ Å, to traverse the hydrophobic thickness of the membrane.

Answer 23

20, 30 Å

Question 24

Evaluate the importance of model systems in understanding the interaction of amyloids with membranes.

Answer 24

Model systems provide simplified platforms to investigate fundamental interactions between amyloids and membranes. These systems allow researchers to control variables, study specific aspects of the interaction, and develop insights that may be challenging in more complex biological environments. While model systems have limitations, their importance lies in providing a foundation for understanding basic principles, guiding further research, and potentially identifying targets for therapeutic interventions. Model systems also facilitate the screening of potential inhibitors or modulators of amyloid-membrane interactions, contributing to drug discovery efforts.

Question 25

The hydrofobicity plot is based on the distribution of amino acids in both __ and __ solvents.

Answer 25

water and organic

Question 26

True/False
Amyloid fibrils in diseases like Alzheimer’s consist of α-helical structures.

Answer 26

False

Question 27

Amyloids are often related to diseases and result from protein _______________.

Answer 27

Misfolding

Question 28

Indicate whether the following statements are true or false:
A. A single α-helix can form a pore.
B. The Meyer-Overton rule accurately predicts the potency of anesthetics.
C. Amyloids are always associated with properly folded proteins.

Answer 28

A-F, B-T, C-F

Question 29

True/False:
Amyloids are soluble and functionally active proteins.

Answer 29

False

Question 30

True/False
Lipid bilayer thickness does not influence the localization of proteins in a membrane.

Answer 30

False

Question 31

Analyze the role of membrane properties in influencing the structure and function of membrane proteins.

Answer 31

Membrane properties, such as fluidity, thickness, and lipid composition, play a vital role in shaping the structure and function of membrane proteins. These properties affect protein localization, conformational changes, and interactions with other molecules. For example, changes in membrane fluidity can impact the dynamics of proteins involved in signal transduction. Understanding the interplay between membrane properties and proteins is essential for unraveling the molecular mechanisms governing cellular processes and developing targeted interventions.

Question 32

Which property is crucial for the activity of cytochrome c oxidase in phosphatidylcholine bilayers?

A. Bilayer thickness
B. Hydrophobicity
C. α-helix content
D. Membrane curvature

Answer 32

A

Question 33

The “Minimal Sensor” for studying thermosensors involves placing active protein parts in a single _______________ segment.

Answer 33

Transmembrane

Question 34

Discuss the limitations and advantages of using the “Minimal Sensor” in studying thermosensors.

Answer 34

The “Minimal Sensor” approach offers advantages and faces limitations in studying thermosensors. One advantage is its simplicity, focusing on essential segments that maintain the sensor’s functionality. This simplicity allows for controlled experiments, aiding in the identification of critical elements involved in temperature sensing. The minimal sensor provides valuable insights into how changes in membrane properties are sensed and transduced. However, its simplicity may also be a limitation, as it might oversimplify the complexity of the native thermosensor’s response in a cellular context. Additionally, the minimal sensor may lack certain regulatory features present in the full-length protein, potentially influencing the accuracy of the obtained data. Care must be taken to ensure that findings from the minimal sensor experiments accurately represent the behavior of the native thermosensor in living cells.

Question 35

True/False
The thickness of the plasma membrane is greater than that of the Golgi membrane.

Answer 35

True

Question 36

What percentage of all genes code for membrane proteins?

a. ~10%
b. ~25%
c. ~50%
d. ~75%

Answer 36

B