Overview
This lecture introduces the fundamentals of protein structure, focusing on the properties, categories, and ionization behaviors of amino acids, and explains how these features impact protein function.
Levels of Protein Structure
- Proteins have four structural levels: primary, secondary, tertiary, and quaternary.
- Primary structure is the amino acid sequence joined by peptide bonds.
- Secondary, tertiary, and quaternary structures involve interactions between amino acids at increasing distances.
- Structure determines protein function, as seen in examples like PCNA protein and viral self-assembly.
Amino Acids: Basics and Stereoisomerism
- Proteins are built from 20 common amino acids; a 21st is found occasionally.
- Amino acids in biological proteins are almost exclusively the L form due to enzyme specificity.
- Each amino acid has a central (alpha) carbon attached to an amine, a carboxyl, a hydrogen, and a unique R group.
Amino Acid Categories
- Hydrophobic amino acids have side chains that avoid water and affect protein folding.
- Polar amino acids have side chains capable of hydrogen bonding or partial ionization, making them hydrophilic.
- Amino acids with basic (positively charged) R groups include lysine, arginine, and histidine.
- Amino acids with acidic (negatively charged) R groups include aspartic acid and glutamic acid.
Ionization and pKa Concepts
- All amino acids have at least two ionizable groups: the alpha carboxyl and the alpha amine, each with a specific pKa.
- pH more than one unit below pKa: proton is on; more than one unit above pKa: proton is off.
- Acidic R groups have pKa ~4.4 and are usually negatively charged at pH 7; basic R groups have pKa ~10-11 and are positive at pH 7.
Titration Curves and Zwitterions
- Amino acids can act as buffers and show titration curves with flattening at buffering regions.
- A zwitterion is an amino acid form with zero net charge, containing both positive and negative charges.
- The pI is the pH at which the amino acid’s net charge is zero; pI is the average of the two pKa values surrounding the neutral form.
Peptide Bonds and Protein Chains
- Amino acids link via peptide bonds between the alpha carboxyl of one and the alpha amine of another.
- All proteins have one free amino end and one free carboxyl end; internal groups are involved in peptide bonds.
Key Terms & Definitions
- Primary Structure — Sequence of amino acids in a protein.
- Stereoisomer — Molecules with the same formula but different spatial arrangements (L and D forms).
- R Group — Variable side chain that defines amino acid properties.
- pKa — pH at which half of a group is protonated; indicates ionization tendency.
- Zwitterion — Molecule with equal positive and negative charges, net charge zero.
- pI (Isoelectric Point) — pH at which a molecule's net charge is zero.
- Peptide Bond — Covalent bond joining amino acids in a protein.
Action Items / Next Steps
- Memorize the 20 amino acid names and their categories (hydrophobic, polar, acidic, basic).
- Review figures from the 7th edition textbook for amino acid structures and categories.
- Practice calculating pI and predicting charges at different pH using pKa values.
- Attend recitations to work through titration plots and charge calculations.