Amino Acids Proteins Part II Dr Kevin Ahern

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Amino Acids & Proteins Part II Dr. Kevin Ahern

Amino Acids & Proteins Part II Dr. Kevin Ahern

From Amino Acids to Proteins Peptide Bonds In Ribosomes Alpha Carboxyl Alpha Amine

From Amino Acids to Proteins Peptide Bonds In Ribosomes Alpha Carboxyl Alpha Amine

Primary Protein Structure Linear sequence of amino acids Joined by Peptide Bonds Translated from

Primary Protein Structure Linear sequence of amino acids Joined by Peptide Bonds Translated from m. RNA using Genetic Code Synthesis begins at amino end and terminates at carboxyl end • Ultimately determines all properties of a protein • •

Polypeptides Alternating Orientations of R-groups A simple view Peptide Bond Free Carboxyl Group Peptide

Polypeptides Alternating Orientations of R-groups A simple view Peptide Bond Free Carboxyl Group Peptide Bond Amino Terminus Carboxyl Terminus Free Alpha Amine Peptide Bond Alternating Orientations of R-groups

Peptide Bonds Chemical Character Double Bond Behavior Alpha Carbons Usually Trans-oriented

Peptide Bonds Chemical Character Double Bond Behavior Alpha Carbons Usually Trans-oriented

Proteins Alpha Carbons Trans Steric Hindrance Separated bulky groups Interacting Bulky Groups Alpha Carbons

Proteins Alpha Carbons Trans Steric Hindrance Separated bulky groups Interacting Bulky Groups Alpha Carbons Cis Separated bulky groups

Polypeptides Multiple Peptide Bond Planes Free Rotation

Polypeptides Multiple Peptide Bond Planes Free Rotation

Phi and Psi Angles Phi Angle Psi Angle Peptide Bond Omega Angle

Phi and Psi Angles Phi Angle Psi Angle Peptide Bond Omega Angle

Ramachandran Plot Bond Angles Primary Angles of Stability

Ramachandran Plot Bond Angles Primary Angles of Stability

Secondary Structure Alpha Helix

Secondary Structure Alpha Helix

Secondary Structure Alpha Helix Hydrogen bonds stabilize structure

Secondary Structure Alpha Helix Hydrogen bonds stabilize structure

Secondary Structure Hydrogen Bonds Beta Strands / Beta Sheets Anti-Parallel

Secondary Structure Hydrogen Bonds Beta Strands / Beta Sheets Anti-Parallel

Beta-Sheet Interactions

Beta-Sheet Interactions

Secondary / Supersecondary Structures

Secondary / Supersecondary Structures

Ramachandran Plot Labeled

Ramachandran Plot Labeled

Secondary Structure Fibrous Proteins • Collagen • Connective tissue • Keratin • Hair /

Secondary Structure Fibrous Proteins • Collagen • Connective tissue • Keratin • Hair / nails • Fibroin • Silk

Collagen Primary Structure Hydroxyproline Proline in Helix Abundant Glycine Occasional Lysine Partial Sequence

Collagen Primary Structure Hydroxyproline Proline in Helix Abundant Glycine Occasional Lysine Partial Sequence

Structural Proteins Keratins Fibrous 50 in Humans Intermediate Filaments of Cytoskeleton Hair, nails, horns

Structural Proteins Keratins Fibrous 50 in Humans Intermediate Filaments of Cytoskeleton Hair, nails, horns

Fibroin Silk Beta sheets Repeating glycines

Fibroin Silk Beta sheets Repeating glycines

Secondary Structure Types Alpha Helix Beta Strands / Beta Helix Reverse turns (5 types)

Secondary Structure Types Alpha Helix Beta Strands / Beta Helix Reverse turns (5 types) 310 Helix

Secondary Structure Tendencies of Amino Acids High Propensity for Alpha Helices High Propensity for

Secondary Structure Tendencies of Amino Acids High Propensity for Alpha Helices High Propensity for Beta Strands High Propensity for Reverse Turns

Amino Acid Hydropathy

Amino Acid Hydropathy

Soluble vs. Membrane Bound Proteins Hydrophobic Amino Acid Bias Inside Hydrophilic Amino Acid Bias

Soluble vs. Membrane Bound Proteins Hydrophobic Amino Acid Bias Inside Hydrophilic Amino Acid Bias Outside Hydrophobic Amino Acid Bias In Bilayer Hydrophilic Amino Acid Bias Outside of Bilayer

Metabolic Melody Oh Little Protein Molecule (To the tune of "Oh Little Town of

Metabolic Melody Oh Little Protein Molecule (To the tune of "Oh Little Town of Bethlehem") Oh little protein molecule You're lovely and serene With twenty zwitterions like Cysteine and alanine Your secondary structure Has pitches and repeats Arranged in alpha helices And beta pleated sheets The Ramachandran plots are Predictions made to try To tell the structures you can have For angles phi and psi And tertiary structure Gives polypeptides zing Because of magic that occurs In protein fol-ding Copyright © Kevin Ahern A folded enzyme’s active And starts to catalyze When activators bind into Its allosteric sites Some other mechanisms Control the enzyme rates By regulating synthesis And placement of phosphates And all the regulation That's found inside of cells Reminds the students learning it Of pathways straight from hell So here’s how to remember The phosphate strategies They turn the GPb's to a's And GSa's to b's

Reverse Turns

Reverse Turns

Tertiary Structure Folding and Turns Beta Strands Alpha Helices Random Coil Turns

Tertiary Structure Folding and Turns Beta Strands Alpha Helices Random Coil Turns

Folding of a Globular Protein

Folding of a Globular Protein

Unfolding of a Globular Protein

Unfolding of a Globular Protein

Forces Stabilizing Tertiary Structure Hydrogen Bonds

Forces Stabilizing Tertiary Structure Hydrogen Bonds

Forces Stabilizing Tertiary Structure Disulfide Bonds (Covalent)

Forces Stabilizing Tertiary Structure Disulfide Bonds (Covalent)

Forces Stabilizing Tertiary Structure

Forces Stabilizing Tertiary Structure

Denaturing/Unfolding Proteins Break forces stabilizing them Mercaptoethanol/dithiothreitol - break disulfide bonds Detergent - disrupt

Denaturing/Unfolding Proteins Break forces stabilizing them Mercaptoethanol/dithiothreitol - break disulfide bonds Detergent - disrupt hydrophobic interactions Heat - break hydrogen bonds p. H - change charge/alter ionic interactions Chelators - bind metal ions

Denaturing/Unfolding Proteins

Denaturing/Unfolding Proteins

Folding of a Globular Protein

Folding of a Globular Protein

Energetics of Folding

Energetics of Folding

Protein Structural Domains Leucine Zipper - Prot. -Prot. and Prot. -DNA Helix Turn Helix

Protein Structural Domains Leucine Zipper - Prot. -Prot. and Prot. -DNA Helix Turn Helix - Protein-DNA Leucine Zipper Zinc Fingers SH 2 Domains - Protein-Protein Pleckstrin Homology Domains - Signaling (Membrane) Zinc Finger Helix-Turn-Helix Leucine Zipper SH 2 Domain Pleckstrin Domains

Folding Errors

Folding Errors

Prion Replication Model

Prion Replication Model

Amyloids and Disease Amyloids - a collection of improperly folded protein aggregates found in

Amyloids and Disease Amyloids - a collection of improperly folded protein aggregates found in the human body. When misfolded, they are insoluble and contribute to some twenty human diseases including important neurological ones involving prions. Amyloid diseases include (affected protein in parentheses) - • Alzheimer’s disease (Amyloid β) • Parkinson’s disease (α-synuclein) • Huntington’s disease (huntingtin), • Rheumatoid arthritis (serum amyloid A), • Fatal familial insomnia (Pr. PSc)

Protein Processing Chaperonins - Proper folding - environment for hydrophobic sequences Gro. EL /

Protein Processing Chaperonins - Proper folding - environment for hydrophobic sequences Gro. EL / Gro. EL-Gro. ES Proteasomes - Degradation to oligopeptides of about 8 amino acids each

Role of Ubiquitin Flag for protein destruction by proteasome

Role of Ubiquitin Flag for protein destruction by proteasome

Intrinsically Disordered Proteins Not all proteins folded into stable structures Intrinsically Disordered Proteins (IDPs)

Intrinsically Disordered Proteins Not all proteins folded into stable structures Intrinsically Disordered Proteins (IDPs) have regions favoring disorder IDP regions tend to lack hydrophobic residues Rich in polar amino acids and proline IDPs may favor adaptation to binding another protein IDPs may favor being modified IDPs may be more involved in signaling and regulation Non-IDPs more involved in catalysis and transport Metamorphic Proteins May adopt more than one stable structure Lymphotactin - monomeric receptor. Binds heparin as dimer

Protein Structure • Primary – Amino Acid Sequence • Secondary / Supersecondary – Repeating

Protein Structure • Primary – Amino Acid Sequence • Secondary / Supersecondary – Repeating Structures – short range forces • Tertiary – Folded structures – longer range interactions

Metabolic Melody My Old Enzymes (To the tune of "Auld Lang Syne") Copyright ©

Metabolic Melody My Old Enzymes (To the tune of "Auld Lang Syne") Copyright © Kevin Ahern Whene’er my proteins go kaput If they are past their prime. The cells will act to soon replace All of my old enzymes They know which ones to break apart Ubiquitin’s the sign A marker for pro-TE-a-somes To find the old enzymes These soon get bound and then cut up In pieces less than nine More chopping yields the single ones Building blocks from old enzymes So in a way the cell knows well Of father time it’s true Amino acids when reused Turn the old enzymes to new