Protein Structure and Amino Acids

1. Amino Acids: The building blocks of proteins. There are 20 standard amino acids categorized into three groups:

   • Essential Amino Acids: Cannot be synthesized by the body and must be obtained through diet (e.g., leucine, lysine, tryptophan).

   • Non-Essential Amino Acids: Can be made by the body (e.g., alanine, aspartic acid, glutamic acid).

   • Conditional Amino Acids: Typically non-essential but can become essential in times of stress or illness (e.g., arginine, cysteine, glutamine).

2. Peptide Bonds: Amino acids are linked together by peptide bonds, formed through a dehydration reaction between the amino group (NH2) of one amino acid and the carboxyl group (COOH) of another. This process forms a polypeptide chain.

3. Protein Structure: Proteins have four levels of structure:

   • Primary Structure: The sequence of amino acids in a polypeptide chain.

   • Secondary Structure: Local folding into structures such as alpha helices and beta sheets due to hydrogen bonding.

   • Tertiary Structure: The overall 3D shape of a polypeptide, formed by interactions between side chains (R groups).

   • Quaternary Structure: The assembly of multiple polypeptide chains into a functional protein complex.

4. Functions of Proteins:

   • Enzymatic activity

   • Structural support

   • Transportation and storage of molecules

   • Regulation (hormones)

   • Immune response (antibodies)

5. Denaturation: The process where proteins lose their structure due to external factors (high temperature, pH changes, etc.), leading to loss of function.

6. Importance of Protein Folding: Proper folding is critical for protein function, and chaperone proteins assist in this process. Misfolded proteins can lead to diseases (e.g., Alzheimer's, cystic fibrosis).

Structure of Amino Acids

• Central/Alpha Carbon: This carbon is the core of the amino acid structure to which all other groups are attached.

• Amino Group (NH2): A functional group consisting of a nitrogen atom attached to two hydrogen atoms, making the amino acid basic.

• Carboxyl Group (COOH): A functional group that makes the amino acid acidic, comprising a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (–OH).

• R Group (Side Chain): A variable group connected to the central carbon that defines the specific characteristics of each amino acid. The R group can vary in size, shape, polarity, and charge, influencing the properties and functions of the protein.

In summary, the basic structure of an amino acid consists of the central carbon attached to an amino group, a carboxyl group, a hydrogen atom, and a unique side chain (R group).

This structural design is essential for the formation of peptide bonds and the overall three-dimensional configuration of proteins.

Dehydration in the context of amino acids refers to the process involved in forming peptide bonds. In this process, a dehydration reaction occurs when the amino group (NH2) of one amino acid reacts with the carboxyl group (COOH) of another amino acid. During this reaction, a molecule of water (H2O) is released, allowing the two amino acids to bond together to form a peptide. This is a crucial step in building proteins, as it links amino acids into polypeptide chains.

Proteins are the functional units of cells

Nearly every dynamic function of a living being depends on proteins. Some examples of protein functions include:

1. Structural support (e.g. collagen in connective tissue)

2. Enzymatic activity (e.g. amylase, which breaks down starch)

3. Transport (e.g. hemoglobin for oxygen transport)

4. Storage (e.g. casein in milk and ovalbumin in egg whites)

5. Signal transduction (e.g. insulin for regulating glucose levels)

6. Immune response (e.g. antibodies that protect the body from pathogens)

The human genome encodes tens of thousands of different proteins with distinct structures and functions.

Amino acids: the building blocks of proteins
An amino acid is an organic molecule that serves as the building block of proteins. Amino acids have a general structure that consists of four components:

1. A central carbon atom (α-carbon)

2. A basic amino group (–NH₂)

3. An acidic carboxyl group (–COOH)

4. A side chain (R group) which gives each amino acid its unique properties.
   

There are 20 amino acids which can be found in the proteins of living organisms. 

The physical and chemical properties of each amino acid determine its functional role within a polypeptide.

Amino acids can be joined together through peptide bonds, which are formed by dehydration (a.k.a. condensation) reactions. 

A molecule made of many amino acids linked together is called a polypeptide (proteins may contain one or more polypeptide chains).

Creating and destroying proteins
Polypeptides are formed by ribosomes in a process called translation. They can be broken down (hydrolyzed) by special enzymes called proteases.

Levels of protein structure
A protein’s specific structure determines how it works. In almost all cases, the function of a protein depends on its ability to recognize and bind to some other molecule.
sequence → structure → function

Proteins have four distinct levels of structure that determine their overall shape and function. 

These levels, known as primary, secondary, tertiary, and quaternary structures, describe how a protein's amino acid sequence folds and interacts to create a functional molecule

Levels of protein structure: primary structure
The primary structure describes the linear sequence of amino acids in a polypeptide chain, linked by peptide bonds. 

Levels of protein structure: secondary structure
The secondary structure describes local folding patterns within the polypeptide chain, stabilized by hydrogen bonds between the backbone atoms (not the sidechains). The most common types of secondary structures are: α-helix and β-pleated sheets.

Levels of protein structure: tertiary structure
The tertiary structure describes the overall shape of a polypeptide resulting from interactions between the side chains of the various amino acids.

Side chain interactions include:

1. Hydrophobic interactions

2. Ionic bonds

3. Hydrogen bonds

4. Disulfide bridges (covalent bonds)
   

Levels of protein structure: quaternary structure
Some proteins have more than one polypeptide subunit. Quaternary structure is the overall protein structure that results from the aggregation of these subunits.

Globular and fibrous proteins

A protein whose molecules curl up into a ‘ball’ shape, such as hemoglobin, is known as a globular protein. 

Globular proteins usually curl up so that their non-polar, hydrophobic R groups point toward the center of the molecule and the polar, hydrophilic R groups point out towards the surface, making them water soluble.

Fibrous proteins are usually not soluble in water and typically have structural roles. Examples of fibrous proteins include keratin and collagen. 

Hemoglobin
Oxygen carrying protein found in red blood cells

• Made of four polypeptide chains

  • 2 α-globin

  • 2 β-globin
    
    

• Each globin has a ‘haem’ group

  • “Prosthetic group” - permanent, tightly bound molecule not made of amino acids

  • Contains iron, which binds to the oxygen

Sickle Cell Anemia
In the genetic condition known as sickle cell anaemia, one amino acid which occurs in the surface of the β chain is replaced with a different amino acid.

At position 6: Glutamate → Valine

Having a non-polar R group on the outside of the molecule makes the haemoglobin much less soluble, causing it to aggregate and change the overall shape of the red blood cells.

Collagen
Collagen is the most common protein found in mammals (~25% of all protein)

• Found in skin, tendons, cartilage, bones, teeth , and walls of blood vessels.
  
  

• Consists of three polypeptide chains, each in the shape of a helix (note: not an alpha helix)

  • These three strands are held together by hydrogen bonds and covalent bonds
    
    

• Covalent bonds link the three-stranded collagen molecules to each other into even larger strands called fibrils
  

Many fibers lie alongside each other and form strong bundles called fibres.

Protein structure bond summary
Primary structure: peptide bonds between amino acids (covalent bonds)

Secondary structure: hydrogen bonds between the backbones of amino acids

Tertiary structure: hydrophobic interactions, hydrogen bonds, ionic bonds, disulfide bridges (covalent bonds) between side chains of amino acids within a single polypeptide chain

Quaternary structure: hydrophobic interactions, hydrogen bonds, ionic bonds, disulfide bridges (covalent bonds) between side chains of amino acids between two or more polypeptide chains