Proteins and Polypeptides: Structure and Function

Module 4: Proteins

• Proteins are biological molecules composed of amino acids (aa's).
• Proteins are essential to life and have diverse functions like structure and catalyzing reactions.
• Proteins contain the elements hydrogen, carbon, oxygen, nitrogen, and sulfur (sometimes).

Amino Acids and Protein Structure (Part A)

• Amino acids are the building blocks of proteins.
• There are 20 standard amino acids.
• Each amino acid has a central carbon atom bonded to an amino group, a carboxyl group, a hydrogen atom, and a variable side chain (R group).
• The R group determines the specific properties of each amino acid (polarity, acidity, and basicity).
• Some amino acids are essential, meaning they must be obtained through diet.
• Amino acids are linked together by peptide bonds through a dehydration reaction.

Protein Monomers: Amino Acids (aa's)

• Amino acids are the building blocks of proteins.
• 20 standard amino acids all with similar structure.
• Amino acids include an amine group (NH2) and carboxylic acid group (COOH).
• The side chain determines properties.
• Half of amino acids are 'essential' for humans, meaning we can't produce them.

Amino Acids are Joined by Peptide Bonds

• Amino acids join to form chains via peptide bonds.
• Peptide bonds form via condensation reaction; water is lost.
• Amino acids are linked end-to-end via peptide bonds, forming a polypeptide.

Peptide Bonds are Usually cis/trans

• In biological proteins peptide bonds are almost always in trans form.
• This is due to steric hindrance which makes cis configuration unfavorable.

Protein Peptides

• Protein dimers, trimers and oligomers are formed from amino acids linked together by peptide bonds.
• Peptides (like the polymers) do not branch; the linkages are linear.
• Peptides are formed by condensation reaction.

Protein Polymers: Biological Proteins

• Polypeptide chains of more than 50 aa's are considered proteins.
• Biological proteins typically contain hundreds of amino acids.
• Multiple proteins can be bonded together to form complex structures with folds or turns.
• Protein folding usually results in a compact, globular shape.

Amino Acid Functional Groups

• Amino acids have an amino terminus and a carboxyl terminus.
• The side chain (R group) determines an amino acid's properties (polarity).

Zwitterions

• Zwitterions are a form that amino acids can exist in, with both positive and negative charges.
• Amino acids are zwitterions at a neutral pH.

Amino Acid and Protein Polarity

• Polarity varies in amino acids, particularly along the side chains.

Amino Acids (by Classification)

• Amino acids are classified based on polarity and acidity/basicity of the side chain (R group).

Amino Acids (Non-polar)

• Nonpolar amino acids typically consist of carbon and hydrogen atoms.
• Nonpolar amino acids often have hydrophobic interactions.

Amino Acids (Polar, Neutral)

• Polar amino acids contain functional groups like hydroxyl (OH) or sulfide (SH).

Amino acids (Polar, Basic, or Acidic)

• Basic amino acids have positive charges at neutral pH.
• Acidic amino acids have negative charges at neutral pH.

Essential vs. Non-essential Amino Acids

• Eight essential amino acids for adults; 10 for children are required in daily diets.
• Nonessential amino acids can be produced in the human body.

Complete vs. Incomplete Protein Sources

• Complete proteins contain all essential amino acids.
• Animal proteins are typically complete.
• Plant proteins are usually incomplete.

Other Uses for aa's

• Some amino acids have functions beyond protein structure.
• For example, tryptophan synthesizes hormones as well as neurotransmitters.

Protein Synthesis: aa's → protein

• The process of protein synthesis involves linking amino acids together.
• The first level (1°) of protein structure is governed by DNA.
• Protein structure is determined by the sequence of amino acids.

Protein Structure

• Proteins have four levels of structure: primary, secondary, tertiary, and quaternary.
• Primary structure is the amino acid sequence.
• Secondary structure involves the folding of the polypeptide chain into a helix or sheet.
• Tertiary structure is the overall 3D shape of the protein.
• Quaternary structure is the arrangement of multiple interacting protein subunits.

1º Structure of Proteins

• Arrangement of amino acids in the polypeptide defines the protein's chemical structure.
• This structure is determined by DNA sequences (with the help of mRNA sequences).

2º Structure of Proteins (a-helix and b-pleated sheet)

• Hydrogen bonds between the backbone of the polypeptide chain stabilize the secondary structure.
• The secondary structures include alpha-helices (spiral) and beta-pleated sheets (folded).

2º Structure: The α-Helix

• A typical alpha-helix is ~10 amino acids long.
• The helix is right-handed and has 3.6 amino acids per turn.
• The peptide bond's C=O bonds hydrogen bond with the N-H of the fourth amino acid.

2º Structure: The β-Pleated Sheet

• Beta-pleated sheets can be parallel or antiparallel.
• Hydrogen bonds between adjacent chains contribute to the pleated sheet structure.
• The side chains of amino acids that form the pleated-sheet arrange alternately.

3º Structure of Proteins

• The 3D shape of the polypeptide chain arises from interactions between side chains (R groups).
• Interactions include disulfide bonds, hydrogen bonds, salt bridges, and hydrophobic interactions.

4 Main Forces holding 3º Protein Structure

• Disulfide bonds form between cysteine amino acids.
• Hydrogen bonds form between polar side chains.
• Salt bridges form between positively and negatively charged side chains.
• Hydrophobic interactions occur between nonpolar side chains.

4º Structure of Proteins

• This structures forms when multiple peptide chains join to form a functional protein.
• Often proteins combine with other protein subunits to form complex shapes.
• The forces that help to shape the protein are the same as those that contribute to 3º structure.

Antibody (Immunoglobulin) 4º structure

• Antibodies have a specific 4º structure, with disulfide bonds.
• Antibodies have specific components or regions, such as the antigen-binding region and constant region.
• Antibodies play a key role in the immune system by binding to and neutralizing pathogens.

4º Protein Example -- NAD(P)H oxidase

• This enzyme's subunits associate and dissociate in coordination with activation.

Protein Denaturation

• Denaturation disrupts the 2º, 3º, and 4º protein structure; the 1º structure remains.
• Denaturation can occur through physical methods such as heat, or through the chemical interaction with other agents like acids or bases.

Denatured Protein: Fried Egg

• Albumin is the protein found in eggs.
• Heat denatures albumin, making the egg white opaque and hard.

Static and Dynamic Proteins (Part B)

• Dynamic proteins are not fixed in one location.
• Static proteins are fixed at a specific location in the body.

Serum Albumins (dynamic)

• They maintain osmotic pressure, transport non-polar molecules.

Globulins (dynamic)

• They're involved in transporting various molecules within the blood, and binding/eliminating foreign molecules (ie antibodies)

Hemoglobin

• Located in red blood cells.
• Contains heme prosthetic group, which is involved with oxygen transport.
• It comprises of 4 subunit polypeptide chains held together by weak interactions.

Myoglobin

• Located in muscle cells.
• Binds to oxygen and stores it for muscle function.
• A monomer, and not a part of blood plasma.

Dietary Protein

• 50% of our body mass comes from protein.
• Dietary intake is vital for the construction of body mass.
• Complete proteins are ideal.

Protein Sources

• Different foods contain differing quantities of protein.
• Meat, poultry, dairy, eggs, and legumes are good protein sources.
• Vegetable sources are also essential.

Protein Intake Recommendations

• Protein needs vary by age, activity level, and other factors.
• Most adults need ~ 10-35%.

‘New’ Canada Food Guide (2019)

• Provides guidance on protein intake, as part of a balanced diet.

How Much Protein Do We Really Need?

• The recommended daily allowance for protein intake is based on body mass and activity.

Collagen (static)

• Collagen is the most abundant protein in mammals and plays a key role in tissue structure.
• Cross-linked and stabilized by hydrogen bonds.
• Important component of skin and connective tissues.

Elastin (static)

• Elastin provides elasticity to tissues like skin, lungs, and arteries.
• Cross-linked via disulfide bonds between cysteine amino acids.
• Its loss with aging leads to tissue sagging.

Proteoglycans (static)

• These proteins are found in connective tissues and provide hydration and support.
• They consist of a core protein with multiple side chains.

Fibronectin (static)

• Fibronectin acts as a connecting protein in connective tissues, including joints, skin and various other tissues.
• Important in processes requiring cell adhesion.

Actin and Myosin (static/dynamic) (both)

• Myosin and Actin are major components of muscle cells.
• Important in muscle contractions.

Protein in Different Cell Environments (example)

• Proteins act in a variety of functions within and outside cells, affecting important processes.

Explore the distinctions between proteins and polypeptides, focusing on amino acid properties, peptide bond formation, and the role of R-groups in protein structure. Understand the classification of polypeptides based on amino acid count and the functions of extracellular matrix components like fibronectin and proteoglycans.