Cytokines: A Primer, Cytokines as Proteins, Cytokines

Cytokines: A Primer, Cytokines as Proteins, Cytokines are Proteins

Cytokines: A Primer, Cytokines as Proteins, Proteins are Linear Polymers of Amino Acids

Cytokines: A Primer, Cytokines as Proteins, Proteins are the Products of Genes

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Temperature

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Addition of Acid

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Addition of Alkali

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Denaturation

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Amino Acids

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Molecular Interactions

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Levels of Structure

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Conditions that Affect Protein Structure

Cytokines: A Primer, Cytokines as Proteins, Protein Structure and Stability: Oxidizing or Reducing Agents

Cytokines

• A class of intercellular signaling molecules

Cytokines

• Proteins that act as messengers between cells
• Especially important for the immune system

Proteins are Linear Polymers of Amino Acids

• Molecules made up of chains of smaller units called monomers joined head-to-tail by strong covalent bonds
• Complex machinery in the cell translates DNA into protein

Amino Acids

• Monomers of the protein polymer 
• Linked by peptide bonds to form the polypeptide chain
• Any one of 20 amino acids may be incorporated into each position of the polypeptide chain
• Each point is determined by the gene that codes for the protein

Proteins are the Products of Genes

• Information specifying any particular protein molecule is contained within a specific gene
• Information encoded in molecules of DNA, which make up the chromosomes found in the nucleus

Increasing temperature causes

• The atoms of the protein molecule to move around more and more
• A protein's native structure can be disrupted
  • Denaturation

Addition of acid to a protein solution

• Causes several side chains that are normally negatively charged to lose their charge
• Other amino acids that were previously uncharged may become positively charged
• Affects the surface of the protein, and may completely alter the structure
• Higher concentrations of acid can promote cleavage of the polypeptide chain

Low concentrations of alkali

• Alter the three-dimensional structure of the polypeptide by changing the charge of its amino acid side chains

High concentrations of alkali

• Able to cleave the polypeptide chain

Denaturation

• Chemical properties of a protein's surface are altered
• Disrupts or completely abolishes a protein's normal interactions with other molecules

Amino Acids

• Polypeptide is a flexible molecule
• Doesn't remain extended
• Folds into a precise three-dimensional structure

Protein's native form

• One stable conformation for the polypeptide in its natural environment within a cell

Side chain

• Branches off the main chain of the polypeptide
• Chemical properties specific to the particular amino acid
• Bear a positive or negative electric charge, or uncharged
• Repelled by water or affinity for water molecules
• End up on the surface of the protein affect the chemical characteristics of the region of the surface at which they are found

Pairs of Amino Acids

• May form a strong ionic interaction within a protein
• May form a strong covalent bond in which two sulfur atoms are joined, creating a disulfide bridge across the protein

Molecular Interactions

• Pockets or other surface shape features may fit and bind to a target molecule
• Charged or water-repelling side chains may be located in just the right spots on the surface to maximize binding or promote a chemical reaction

Interactions between amino acids

• Aren't directly joined within an individual protein chain
• Weaker than the covalent bonds that hold the amino acids together head-to-tail in the chain
• Thus, it's difficult to break the protein up into its constituent amino acids
• Allows a single protein molecule to bind to and affect many other target molecules

Levels of Structure

Primary Structure

• Sequence of amino acids

Secondary Structure

• Regions of the protein chain that take on structures such as alpha helices and beta sheets

Tertiary Structure

• Secondary structures that assemble into organized bunches to form domains

Quaternary Structure

• Level of structure describing spatial arrangement of two or more polypeptide chains in a complex

Characteristics of the solution in which a protein molecule is

• Dissolved
• In a cell
• In the bloodstream
• In a vial

Surrounding conditions affect the characteristics and sometimes the structure of a given protein.

Oxidizing or reducing agents

• Affects the side chains of some amino acids, particularly cysteine

Diatomic oxygen from the air can be transformed into highly reactive oxygen species

• Peroxides
• Free radicals

Reactive oxygen species

• Generated by exposing a solution to light

Peroxides and free radicals

• Present in the formulation excipients

Cysteine

• Side chain can be oxidized by reactive oxygen species, prevents it from forming a disulfide bond

Disulfide

• Can be broken by reducing agents like mercaptans.
• Reducing agents can be generated by breakdown of additives to protein solutions such as surfactants