Protein Quality Control

What are the primary functions of protein quality control systems?

They assist in protein folding and manage the degradation of misfolded or damaged proteins.

What can happen if a protein fails to fold correctly?

It may form disordered aggregates or highly ordered amyloid fibers.

What is the role of the Ubiquitin Proteasome Complex (UPS)?

It degrades misfolded proteins from the cytoplasm and the endoplasmic reticulum (via ERAD).

How are larger protein aggregates typically degraded?

Through the process of autophagy.

What is the consequence for a cell if protein quality control systems fail?

The cell may undergo apoptosis, or programmed cell death.

How does the half-life of defective proteins compare to long-lived proteins like hemoglobin?

Defective proteins are generally short-lived, whereas proteins like hemoglobin are long-lived.

To which part of a target protein is ubiquitin covalently attached?

The Lysine (Lys) side chain.

What are the three enzymes involved in the attachment of ubiquitin to a target protein?

E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligating enzyme).

What is polyubiquitin and what is its primary function?

It is a covalent polymer of ubiquitin subunits that targets the attached protein for destruction in the proteasome.

Describe the structure of the proteasome.

It is a large complex consisting of four rings forming a barrel, containing several proteases with different substrate specificities.

What is the 'N-end rule' in protein degradation?

The rate of protein degradation is governed by the recognition of the N-terminal amino acid, which helps determine the protein's half-life.

Where are Lon proteases primarily located in eukaryotic cells?

In the mitochondrial matrix.

What is the function of the ClpS protein in bacteria?

It binds to exposed N-end rule residues and tethers the substrate to the ClpAP protease for degradation.

How are SsrA-tagged proteins generated in bacteria?

They are produced when ribosomes stall during the translation of mRNAs with nonsense mutations, leading to the cotranslational attachment of the ssrA peptide via the tmRNA pathway.

Which adaptor protein recognizes the ssrA tag and delivers the protein to ClpXP?

The SspB adaptor.

What is the general role of chaperones in protein quality control?

They help proteins fold, stay folded, refold, and assemble into multimeric complexes.

What happens to a substrate protein upon binding to the GroEL chaperonin?

It undergoes local unfolding into an ensemble of expanded and compact conformations.

What role does ATP play in the GroEL/GroES folding cycle?

ATP-dependent domain movement of the apical GroEL domains stretches tightly bound regions of the substrate and promotes partial compaction.

What is the function of the GroES cap in the GroEL/GroES system?

It encapsulates the substrate, allowing for folding within the protected chaperonin cage.

What is the difference between the 'cis' and 'trans' rings of the GroEL complex?

The 'cis' ring is the GroES-bound chamber where active folding occurs, while the 'trans' ring is the opposite, unbound ring.

Are N-end rule residues typically exposed in normally synthesized proteins?

No, they are usually shielded and only become exposed following processing or cleavage.

What is the chemical nature of the bond formed between ubiquitin and the target protein?

An amide (isopeptide) bond.

What is the primary characteristic of the ubiquitin protein across eukaryotes?

It is highly conserved.

What is the final step in the GroEL/GroES folding cycle?

Substrate release upon GroES dissociation, with the possibility of rebinding if the protein remains incompletely folded.