9: Structural Proteins and Their Targeting

Question 1

What are structural proteins?

Answer 1

• extracellular matrix components (e.g. collagen)
• transmembrane proteins: link intracellular with extracelluar (integrins)
• intraceullular structural components (tubulin, actin, intermediate filaments)

Question 2

What are some intracellular proteins?

Answer 2

• microtubules (largest)
• intermediate filaments (medium)
• actin (smallest)

Question 3

Describe tubulin

Answer 3

• structural protein that is essential for M phase of the cell cycle
• inhibition of tubulin will inhibit cell division

Question 4

Alpha tubulin is bound by…

Answer 4

GTP

Question 5

Beta tubulin is bound by…

Answer 5

GDP

Question 6

How would tubulin work as a drug target?

Answer 6

interrupting the cell cycle of highly proliferative cells (fight cancer cells and infectious diseases)

Question 7

What do alpha and beta tubulin form?

Answer 7

they form protofilaments (rows of alternating alpha and beta subunits)

Question 8

what do protofilaments form?

Answer 8

they form microtubules, involved in mitosis, motility, transport, cell shape

Question 9

How do protofilaments form microtubules?

Answer 9

protofilaments add (polymerize) and dissemble (depolymerize) from the + end of the microtubule while the other end is capped with a capping protein

Question 10

What are the 4 key stages of the cell cycle?

Answer 10

G1 = Gap 1 - duplicates organelles and cytosolic components, starts replicating chromosome

S = synthesis - DNA is replicated

G2 = Gap 2 - cell growth continues, enzymes and proteins are synthesized and replication of centrosomes is completed

Mitosis

Question 11

Why would it be beneficial to target tubulin as a drug target?

Answer 11

tubulin is essential for dividing cells
- you can block assembly/polymerization
- you can block disassembly/depolymerization
- in both cases, cells are arrested in mitosis/G2

Question 12

define cytostatic

Answer 12

cytostatic is when a cell has been arrested from growth but they’re still alive
- accumulation in G2/mitosis phase

Question 13

Explain colchicine and what it would be used for

Answer 13

blocks microtubule assembly
- anti-inflammatory
- inhibits microtubule assembly/polymerization

Question 14

explain vinca alkaloids (vinblastine/vincristine)

Answer 14

block of microtubule assembly
- blocks mitosis
- vinca alkaloid binds to free tubulin dimers and ruins assembly

vinblastine/vincristine - used for chemotherapy of leukemia and lymphoma

Question 15

explain griseofulvin and its function

Answer 15

blocks disassembly
- oral antifungal drug
- stabilizes polymers

Question 16

what effect does paclitaxel/docetaxel (taxol) have on microtubules?

Answer 16

taxol binds tubulin and blocks microtubule disassembly
- tubulin dimers will STAY as microtubules
- used for cancers
- inhibits mitosis interfering with mitotic spindle cell biology
- stabilizes microtubule polymer and prevents a metaphase spindle configuration –> messes with mitotic biology –> abnormal cell division –> kills cell/stops growth