Lecture 8 - Protein Folding III

Question 1

Describe the type of 2* structure associated with aggregated proteins?

Answer 1

Beta-sheets with cross linkage between them

Question 2

______ are proteins that consist of cross-linked beta sheets

Answer 2

Aggregates

Question 3

What are some possible causes of protein mis-folding/beta-sheet production?

Answer 3

Environmental damage/radiation/chemicals, etc.

Question 4

Outline the steps that form the amyloid plaque

Answer 4

Lack of chaperones -> “seeding” or “nucleation”
Nuclei begin to form fibrils (“stringlike” with beta-cross links)
Begin to form “deposits”

Question 5

Protein aggregation is characterized by formation of ______.

Answer 5

insoluble amyloid fibrils

Question 6

Amyloid fibrils are derived from what naturally occurring cell protein?

Answer 6

amyloid precursor proteins (APP)

Question 7

How are mis-folded proteins “marked” for degredation?

Answer 7

Through conjugation with uqiquitin, which marks it for removal by the proteosome.

Question 8

Destroys damaged organelles (normal function) or other mis-folded proteins (when then proteosome is saturated)

Answer 8

authphagosome

Question 9

Aside from seed polymerization, what other ways are proteins subject to aggregation?

Answer 9

Oxidative modification; phosphorylation; Ubiquitin like-SUMOylation; proteolytic cleavage

Question 10

(Large/small) protein aggregates are believed to be responsible for cellular damage in neurodegenerative disease.

Answer 10

small

Question 11

These contain a pocket that binds a metal ion; they then add the correct metal to proteins

Answer 11

metallochaperone

Question 12

What are the three main types of storage/transport metalloproteins?

Answer 12

e- carriers
metal managers
oxygen managers

Question 13

What are the three main types of enzymatic metalloproteins?

Answer 13

Hydroxylases
Oxidoreductases
Isomerases/synthases

Question 14

What is the structure of most “normal” proteins?

Answer 14

alpha-helix

Question 15

3 chars of infectious proteins

Answer 15

• aggregates of a specific protein that is transmissible
• proteins are resistant to dissolving
• completely/largely derived from naturally occurring cell proteins

Question 16

Describe the characteristics of the “amorphorous aggregates” and why they are important to understanding disease.

Answer 16

Amorphorous aggregates have LESS E* and are MORE thermodynamically stable than native proteins; this causes them to “feed” into the pathway that produces amyloid fibrils

Question 17

The lack of what normal cellular mechanism is thought to promote “seeding” or “nucleation” of pro-amyloid fibril type protein structures

Answer 17

A lack of chaperone correction

Question 18

Zn, Pb, and Cd can all lead to _____ of protein folding

Answer 18

inhibition (heavy metal poisoning)

Question 19

Metal ions are required for the correct folding of almost ____ of all proteins.

Answer 19

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