Week 2 Overview

• Week 2 is mainly focused on attendance and upcoming assignments.

• Reminder of the only personal assignment that was due yesterday.

• No lab this week due to missed class on Monday.

• Upcoming first exam covers material from last week and this week, comprising all short answer questions with no multiple choice.

Exam Format

• Six exams scheduled roughly every two weeks.

• Exam format:

  • All questions are short answers, must adhere to the 50-minute in-class time.

Upcoming Assignments

• Two Perusall assignments next week: Tuesday and Thursday.

• Transition into discussing the second biomolecule, lipids, while still covering proteins.

Protein Classification

• Proteins can be categorized into families based on structural and functional similarities.

• Example: Elastase and Chymotrypsin are classified as serine proteases.

  • Both proteins have similar structures, with greater than 50% difference in amino acid sequence.

  • Serine is crucial for their catalytic function in cleaving peptide bonds.

Information Flow in Proteins

• Primary structure is critical; it leads to secondary, tertiary, and quaternary structures.

• Proper information for creating primary structure originates from DNA.

• Changes in DNA can affect the structure and function of proteins:

  • Mutation examples impact primary structure and consequently secondary and tertiary structures.

Key Molecular Processes

• Transcription: Conversion of DNA to RNA.

• Translation: Reading of RNA to synthesize proteins.

  • Ribosomes translate RNA sequences into amino acids, determining primary structure.

• Specific genes (e.g., Gene A and Gene B) show the variability of transcription rates impacting protein levels in cells.

Role of DNA and Transcription

• DNA serves as the information storage molecule, mostly static in the nucleus.

• Its sequence codes for amino acid order in proteins.

  • Mutation (e.g., change from adenine to thymine) can lead to primary structure changes.

  • Example of mutation affecting function: Phenylalanine hydroxylase (PAH) in PKU disease.

Examples and Consequences of Mutations

• PKU caused by a single nucleotide mutation leads to improper PAH enzyme structure.

• PAH enzyme proposed functionality: converting Phenylalanine (essential amino acid) to Tyrosine (non-essential amino acid).

• In rats with PKU, enzyme structure changes affect conversion leading to neurological defects due to phenylalanine accumulation.

Protein Structure and Types

• Understanding quaternary structure exemplified through PAH, requiring four identical polypeptide chains.

  • Each chain possesses primary, secondary, and tertiary structures.

  • The tetramerization domain facilitates the assembly of the functional quaternary structure.

• Mutations alter the structure impacting function due to changes in bonding characteristics involving ionic and hydrogen bonds.

Cellular Mechanisms of Protein Folding

• Protein folding can be problematic due to:

  • Hydrophobic amino acids preferring water-avoiding interactions.

  • Incorrectly formed disulfide bonds requiring enzymes like protein disulfide isomerase for correction.

Chaperone Proteins

• Function to assist misfolded proteins in achieving correct three-dimensional structures.

• Chaperones encapsulate misfolded proteins in a protective hydrophobic barrel allowing for refolding in proper orientation.

• Found in cytoplasm and endoplasmic reticulum (ER).

Conclusion

• Understanding transcription, translation, and folding elucidates the relationship between DNA, protein structure, and function.

• The necessity of proper folding and correct protein structures for functionality is emphasized.

Week 2 Overview

Week 2 focuses primarily on attendance and important upcoming assignments. It serves as a recap of previous content and sets the groundwork for new material.

Attendance Reminder

• A reminder of the only personal assignment that was due yesterday is noted, ensuring all students remain on track with their responsibilities.

• There is no lab this week due to a missed class on Monday, which affects hands-on learning and practical application of the curriculum.

Upcoming Exams

• The first exam of the term is scheduled soon and will cover material presented in the last week as well as this week. It will consist exclusively of short answer questions, eliminating the multiple-choice format.

• Exam Format:

  • A total of six exams will be scheduled roughly every two weeks over the course of the term.

  • Each exam will be formatted with all short-answer questions, requiring students to articulate responses within a strict 50-minute in-class timeframe.

Upcoming Assignments

• Students will have two Perusall assignments to complete next week, specifically on Tuesday and Thursday, which will involve collaborative learning through reading and discussion.

• The course will transition into a discussion on the second biomolecule, lipids, while still covering the topic of proteins to provide a comprehensive understanding of biomolecular structures and functions.

Protein Classification

• Proteins can be categorized into various families based on their structural and functional similarities, enhancing the understanding of their roles in biological processes.

• An example includes Elastase and Chymotrypsin, both classified as serine proteases. Despite having over 50% difference in their amino acid sequences, they share significant structural similarities that contribute to their common catalytic functions.

• The serine amino acid residue is crucial for their enzymatic role in cleaving peptide bonds, highlighting the significance of amino acid composition in protein function.

Information Flow in Proteins

• The primary structure of proteins is critical, as it determines subsequent secondary, tertiary, and quaternary structures, ultimately dictating protein functionality.

• The information required for creating the primary structure originates from DNA, emphasizing the genetic basis of protein synthesis.

• Changes or mutations in DNA can lead to profound effects on the structure and function of proteins, potentially resulting in altered physiological states.

  • Example of Mutations: Variants in DNA sequence can impact primary structure and subsequently influence higher-order structures like secondary and tertiary arrangements.

Key Molecular Processes

• Transcription: This is the process where the DNA sequence is transcribed into messenger RNA (mRNA).

• Translation: This refers to the process where ribosomes read the mRNA sequence to synthesize proteins, determining the primary structure based on codon sequences.

• Specific genes, such as Gene A and Gene B, exhibit variability in transcription rates, which significantly impacts protein levels and functions in cells, suggesting regulatory mechanisms of gene expression.

Role of DNA and Transcription

• DNA functions as the information storage molecule residing primarily in the nucleus, maintaining static sequences that code for the amino acid sequence in proteins.

• A mutation (e.g., a nucleotide change from adenine to thymine) can lead to alterations in primary structure, potentially affecting protein functionality.

• An illustrative mutation impacting function is the alteration in Phenylalanine hydroxylase (PAH) in individuals with Phenylketonuria (PKU) disease.

Examples and Consequences of Mutations

• PKU: Caused by a single nucleotide mutation in the PAH gene, leading to an altered enzyme structure.

• The primary function of the PAH enzyme is to convert Phenylalanine, an essential amino acid, into Tyrosine, a non-essential amino acid.

• In rat models of PKU, the enzymatic structure is compromised, resulting in an inability to convert Phenylalanine, leading to its accumulation which can cause severe neurological defects.

Protein Structure and Types

• Understanding quaternary structure can be exemplified through PAH which necessitates four identical polypeptide chains for proper function.

• Each polypeptide chain possesses its own primary, secondary, and tertiary structures that contribute to the overall functionality of the protein complex.

• The process of tetramerization is crucial, as the functional quaternary structure is assembled through interactions between these polypeptides.

• Mutations in the protein-coding sequence may alter bonding characteristics, impacting ionic and hydrogen bond formations and ultimately influencing protein stability and function.

Cellular Mechanisms of Protein Folding

• Protein folding can be hindered by various factors, particularly due to:

  • Hydrophobic amino acids which prefer to interact in a non-polar environment, leading to misfolded structures in aqueous solutions.

  • Incorrectly formed disulfide bonds, which require specific enzymes, such as protein disulfide isomerase, to correct faulty bonding.

Chaperone Proteins

• Chaperone proteins play a crucial role in assisting misfolded proteins in achieving their correct three-dimensional structures, thereby preventing aggregation and loss of function.

• They function by encapsulating misfolded proteins in protective hydrophobic barrels, facilitating proper refolding in the correct orientation within the cell.

• Chaperones are found notably in the cytoplasm as well as the endoplasmic reticulum (ER), where protein synthesis and folding predominantly occur.

Conclusion

• A comprehensive understanding of the processes of transcription, translation, and folding is essential, as it elucidates the intricate relationship between DNA, protein structure, and their corresponding function in living organisms.

• Emphasizing the necessity for proper folding and the correct three-dimensional structures is vital, as these attributes are key for their functional roles in biological systems.