Describe the type of 2* structure associated with aggregated proteins?
Beta-sheets with cross linkage between them
______ are proteins that consist of cross-linked beta sheets
What are some possible causes of protein mis-folding/beta-sheet production?
Environmental damage/radiation/chemicals, etc.
Outline the steps that form the amyloid plaque
Lack of chaperones -> “seeding” or “nucleation”
Nuclei begin to form fibrils (“stringlike” with beta-cross links)
Begin to form “deposits”
Protein aggregation is characterized by formation of ______.
insoluble amyloid fibrils
Amyloid fibrils are derived from what naturally occurring cell protein?
amyloid precursor proteins (APP)
How are mis-folded proteins “marked” for degredation?
Through conjugation with uqiquitin, which marks it for removal by the proteosome.
Destroys damaged organelles (normal function) or other mis-folded proteins (when then proteosome is saturated)
Aside from seed polymerization, what other ways are proteins subject to aggregation?
Oxidative modification; phosphorylation; Ubiquitin like-SUMOylation; proteolytic cleavage
(Large/small) protein aggregates are believed to be responsible for cellular damage in neurodegenerative disease.
These contain a pocket that binds a metal ion; they then add the correct metal to proteins
What are the three main types of storage/transport metalloproteins?
What are the three main types of enzymatic metalloproteins?
What is the structure of most “normal” proteins?
3 chars of infectious proteins
- aggregates of a specific protein that is transmissible
- proteins are resistant to dissolving
- completely/largely derived from naturally occurring cell proteins
Describe the characteristics of the “amorphorous aggregates” and why they are important to understanding disease.
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
The lack of what normal cellular mechanism is thought to promote “seeding” or “nucleation” of pro-amyloid fibril type protein structures
A lack of chaperone correction
Zn, Pb, and Cd can all lead to _____ of protein folding
inhibition (heavy metal poisoning)
Metal ions are required for the correct folding of almost ____ of all proteins.