9/6 PROTEIN REFOLDING AND DEGRADATION

Commute and Class Logistics

• Commute Details: Discussion about commuting challenges between Illinois and St. Louis, focusing on heavy traffic on major highways.

  • Mention of avoiding I-70 due to congestion.

  • Acknowledgment of how coming from Illinois affects overall commute experience.

• Attendance and Lab Preparation:

  • Labs handouts are distributed ahead of schedule due to upcoming exam.

  • Students reminded to return lab materials on Monday, the same day as the exam.

Exam Information

• First Exam Details:

  • Format: All short answer with no multiple choice or fill-in-the-blanks.

  • Value: Each exam is worth 50 points, designed to be completed within 50 minutes.

  • Reminder of lab session on the same day, requiring proper lab attire (long pants and safety goggles).

Biomolecules and Protein Folding

• Transition to Lipids: Upcoming focus on lipids as the next biomolecule topic, with assignments due on specified dates.

• Protein Folding Process:

  • The ribosome's role in protein synthesis; the primary structure of proteins is created as the ribosome reads RNA.

  • Discusses how hydrophobic interactions significantly influence folding patterns.

Chaperone Proteins

• Role of Chaperones:

  • Serve to assist in proper protein folding, particularly preventing the aggregation of misfolded proteins.

  • Chaperones form a protective environment to enable proteins to reach their lower-energy conformations.

  • Note on the energy cost (ATP usage) associated with chaperone activity.

Unfolded Protein Response (UPR)

• UPR Activation: Occurs when proteins misfold, leading to a cellular response that focuses on refolding or degrading misfolded proteins.

  • Three Main Actions of UPR:

    1. Stop Translation: Halting the production of all proteins except for chaperones.

    2. Increase Chaperone Production: Facilitating the response to misfolded proteins.

    3. ER Expansion: The ER grows to accommodate more proteins needing assistance.

Mechanisms of Degradation

• Proteasome Function:

  • Engages in degrading proteins tagged with ubiquitin, allowing for the selective degradation of misfolded or unnecessary proteins.

  • Proteasome limits degradation to proteins that have been marked, preventing loss of necessary cellular proteins.

• Lysosomes’ Role:

  • Serve as a secondary mechanism to degrade proteins, utilizing a low pH environment to facilitate breakdown.

  • Contains various enzymes that can break down proteins, nucleotides, sugars, and lipids.

Consequences of Protein Misfolding

• Potential Outcomes if UPR Fails:

  • Continued accumulation of misfolded proteins can lead to apoptosis (cell death).

  • Emphasizing the critical nature of correct protein folding for cellular health and function.

Cancer and Apoptosis

• Cancer Connections:

  • Discussion on how mutations can prevent normal pathways like apoptosis from functioning, allowing cancer cells to survive and proliferate.

  • Cancer treatments may aim to induce apoptosis in cancer cells, leading to collateral effects on normal cells.

Case Study Activity

• Group Work: Transition into practical application through a case study regarding protein misfolding, illustrating the concepts covered in class.

  • Instructions given for group dynamics and ensuring everyone participates in the activity.

Commute and Class Logistics

Commute Details

• Commute Challenges: The discussion revolves around the significant commuting challenges faced between Illinois and St. Louis. Heavy traffic frequently plagues major highways, leading to longer travel times and increased stress for commuters.

• Alternative Routes: A specific mention is made regarding the avoidance of I-70 due to persistent congestion, prompting commuters to seek alternative routes to save time.

• Illinois Commute Impact: It's acknowledged that coming from Illinois uniquely affects the overall commute experience, as commuters may encounter additional obstacles that differ from those starting in Missouri.

Attendance and Lab Preparation

• Lab Handouts: To better prepare for upcoming exams, lab handouts are distributed well in advance, facilitating students' understanding of the materials.

• Material Return Reminder: Students receive a reminder about the necessity of returning lab materials on the upcoming Monday, coinciding with the exam date, ensuring that all resources are accounted for.

Exam Information

First Exam Details

• Exam Format: The exam will consist exclusively of short answer questions; there will be no multiple choice or fill-in-the-blank questions, allowing students to showcase their knowledge comprehensively.

• Value and Duration: Each exam is designed to hold a total of 50 points, with an allocated time of 50 minutes for completion.

• Lab Session Reminder: Students are reminded of the lab session scheduled on the same day as the exam, underlining the importance of wearing proper lab attire, specifically long pants and safety goggles, to ensure safety during practical work.

Biomolecules and Protein Folding

Transition to Lipids

• Upcoming Focus: The class will transition to the next biomolecule topic focusing on lipids, with assignments due on specified dates that are communicated to students in advance to aid in their preparation.

Protein Folding Process

• Ribosome's Role: The ribosome plays a critical role in protein synthesis by creating the primary structure of proteins as it reads RNA. This is a fundamental process in cellular biology, as proteins are essential for various functions in living organisms.

• Hydrophobic Interactions: The notes discuss how hydrophobic interactions significantly influence folding patterns of proteins, shaping their three-dimensional structures and ultimately their functionality.

Chaperone Proteins

Role of Chaperones

• Assistance in Folding: Chaperone proteins serve a crucial role in assisting proper protein folding, particularly in preventing the aggregation of misfolded proteins, which can lead to cellular dysfunction.

• Protective Environment: They create a protective environment that enables proteins to reach their lower-energy conformations, significantly improving protein stability and function.

• Energy Cost: It's important to note the energy cost (ATP usage) associated with chaperone activity, which highlights the biological significance and resource investment in maintaining protein integrity.

Unfolded Protein Response (UPR)

UPR Activation

• Misfolded Proteins: The unfolded protein response (UPR) is activated when proteins misfold, leading to a cellular response focusing on either refolding or degrading such proteins to maintain cellular health.

Three Main Actions of UPR

1. Stop Translation: The first action is to halt the production of all proteins except for chaperones, thereby conserving resources while addressing the misfolding crisis.

2. Increase Chaperone Production: Second, there is an increase in chaperone production to facilitate the effective response to misfolded proteins and rectify the folding issues.

3. ER Expansion: Last, the endoplasmic reticulum (ER) expands to accommodate more proteins that require assistance, showcasing the cell's capacity to manage stress.

Mechanisms of Degradation

Proteasome Function

• Proteasome Activity: The proteasome functions by degrading proteins that are tagged with ubiquitin, allowing for selective degradation of misfolded or unnecessary proteins, thus regulating protein turnover in cells.

• Marked Proteins: This mechanism limits degradation to proteins that have been marked, preventing the loss of necessary cellular proteins essential for various biological processes.

Lysosomes’ Role

• Secondary Breakdown Mechanism: Lysosomes provide a secondary mechanism for protein degradation, utilizing a low pH environment that enables breakdown through various enzymes capable of degrading proteins, nucleotides, sugars, and lipids.

Consequences of Protein Misfolding

Outcomes if UPR Fails

• Cell Death: If UPR fails, there can be severe consequences, including the continued accumulation of misfolded proteins that may ultimately lead to apoptosis (cell death).

• Importance of Correct Folding: This emphasizes the critical importance of correct protein folding for maintaining cellular health and function, as misfolded proteins can disrupt normal cellular activities.

Cancer and Apoptosis

Cancer Connections

• Mutations and Apoptosis: A discussion on how mutations can impede normal apoptotic pathways, allowing cancer cells to survive and proliferate uncontrollably.

• Treatment Implications: Cancer treatments may aim to induce apoptosis in cancer cells, but this can lead to collateral effects on normal cells, underlining the need for targeted therapeutic strategies.

Case Study Activity

Group Work

• Practical Application: The class will transition into practical applications through a case study addressing protein misfolding, illustrating the concepts covered during lectures.

• Group Dynamics: Instructions are given for fostering effective group dynamics, ensuring full participation from all members in the activity, enhancing collaborative learning experiences