Biochemistry Free For All Protein Structure Biochemistry Free For All

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

Primary Protein Structure Linear sequence of amino acids Joined by Peptide Bonds Translated from mRNA 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 Alpha Amine Free Carboxyl Group Amino Terminus Carboxyl Terminus

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

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

Polypeptides Multiple Peptide Bond Planes Free Rotation

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

Ramachandran Plot Bond Angles Primary Angles of Stability

Secondary Structure Alpha Helix

Secondary Structure Alpha Helix Hydrogen bonds stabilize structure

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

Beta-Sheet Interactions

Secondary / Supersecondary Structures

Ramachandran Plot Labeled

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

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

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

Fibroin Silk Beta sheets Repeating glycines

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 Reverse Turns High Propensity for Beta Strands

Amino Acid Hydropathy

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

Reverse Turns

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

Folding of a Globular Protein

Unfolding of a Globular Protein

Forces Stabilizing Tertiary Structure Hydrogen Bonds

Forces Stabilizing Tertiary Structure Disulfide Bonds (Covalent)

Forces Stabilizing Tertiary Structure

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

Denaturing/Unfolding Proteins

Folding of a Globular Protein

Energetics of Folding

Protein Structural Domains Leucine Zipper Protein Structural Domains Leucine Zipper - Prot.-Prot. and Prot.-DNA Helix Turn Helix - Protein-DNA Zinc Fingers SH2 Domains - Protein-Protein Pleckstrin Homology Domains - Signaling (Membrane) Leucine Zipper Zinc Finger Helix-Turn-Helix SH2 Domain Pleckstrin Domains

Folding Errors

Prion Replication Model

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 (PrPSc)

Protein Processing GroEL / GroEL-GroES Chaperonins - Proper folding - environment for hydrophobic sequences GroEL / GroEL-GroES Proteasomes - Degradation to oligopeptides of about 8 amino acids each

Role of Ubiquitin Flag for protein destruction by proteasome

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 Structures – short range forces Tertiary – Folded structures – longer range interactions