Native Configuration of Proteins

• Proteins are polymers comprised of amino acids linked by covalent bonds, known as peptide bonds.
• Amino acids arrange into polypeptide chains, folding in space to attain their native configuration.

Native Configuration of Proteins

• The native configuration defines the stable arrangement of atoms within a polypeptide chain.
• The three-dimensional structure of a protein is adopted upon folding.
• It's determined by the amino acid sequence and dictates the biological function of the protein.

Amino Acids

• Amino acids are the monomers constituting proteins.
• They are composed of a central carbon atom (alpha carbon), an amino group, a carboxyl group, a hydrogen atom, and a side chain (R group).
• Most amino acids exhibit chirality at the alpha carbon.
• The side chain, or R group, varies between amino acids and determines chemical and biological properties.

Standard Amino Acids

• There are 20 standard amino acids with biological functions.
• These amino acids combine in various ways to form diverse protein types.
• Besides standard amino acids, proteins may include non-standard amino acids, which result from chemical modifications of standard amino acids.
  • Modifications include hydroxyproline, hydroxylysine, selenocysteine, desmosine, pyrrolysine, and carboxyglutamate.
• Each amino acid within a polypeptide chain is a residue.

Peptide Bond Formation

• Peptide bond formation is a condensation reaction.
• It links the α-amino group of one amino acid to the α-carboxyl group of another, releasing water.
• During peptide bond formation, amino acids lose atoms and are referred to as residues.
• In aqueous solutions at neutral pH, amino acids predominantly exist as dipolar ions or zwitterions.

Structural Levels of Proteins

• Primary structure: The amino acid sequence stabilized by peptide bonds between amino acid residues.
• Secondary structure: Amino acids fold into defined patterns stabilized by hydrogen bonds between atoms forming the peptide bonds.
• Tertiary structure: Achieved through mostly non-covalent interactions between atoms in the amino acid side chains.
• Quaternary structure: Several polypeptide chains unite through mostly non-covalent interactions between atoms forming amino acid side chains.

Protein Motifs and Domains

• Supersecondary structures, or protein motifs, are three-dimensional arrangements adopted by the protein's secondary structure, forming various spatial conformations.
• Protein domains are specific regions of a protein chain characterized by a distinct function.

Protein Classification by Shape

• Fibrous: Form elongated thread-like structures.
• Globular: Have more compact, spherical shapes.

Protein Classification by Composition

• Simple: Proteins that contain only amino acids.
• Conjugated: Have additional chemical components, such as lipids and carbohydrates.

Protein Classification by Number of Chains

• Monomeric: Consist of a single polypeptide chain and possess tertiary structures.
• Multimeric: Composed of multiple subunits exhibiting quaternary structure.
  • Multimeric proteins can be either oligomeric (composed of few subunits) or multimeric (composed of multiple subunits)

Protein Characteristics

• Each protein has a unique amino acid sequence, conferring specific properties.
• Proteins are coded by DNA, making the DNA of each living organism the source for the protein composition.
• Proteomics is the comprehensive examination of all proteins expressed by a genome, i.e., proteome.

Protein Sensitivity

• Proteins are sensitive to pH and temperature changes. Denaturation results in loss of biological activity while renaturation can restore activity.

Protein Distribution & Function

• Proteins are abundant, constituting dry weight of a cell.
• They are distributed widely, including in plasma, cellular membranes, cytosol, and interstitial spaces.
• Proteins demonstrate versatility, and participate in most cellular functions.

Key Protein Functions

• Catalysis
• Transport
• Storage
• Movement
• Structural support
• Protection
• Signal reception
• Hormonal regulation
• Coagulation
• pH buffering
• Osmotic pressure maintenance
• Gene expression regulation

Examples of Biologically Important Proteins-

• Collagen and Elastin
• α-Keratin, Actin F, and Tubulin
• Albumin
• Immunoglobulins

Collagen Structure

• Collagen has a distinct structure.
• It has repeats of glycine-proline-hydroxyproline.
• It also has alpha chains with its triple helix structure.
• Collagen is hierarchical organized from molecule to fiber.
• Proline or Lysine require modification (hydroxylation), which is dependent on vitamin C.
• Collagen content varies across tissues, from 4% in the liver to 90% in demineralized bone.

Collagen Types

• Type I collagen is prevalent in skin, bones, tendons, ligaments, cornea, and teeth.
• Type II collagen forms cartilage, supporting joints, the nose, and ears.
• Type III collagen resides in skin, blood vessels, intestines, the uterus, muscle tissue, and glands.
• Type IV collagen is located in basement membranes.

Collagen Related Illnesses

• Ehlers-Danlos syndromes describes inherited genetic disorders caused by collagen synthesis defects.
  • They involve joint hypermobility, skin hyperelasticity, and tissue fragility.
• Osteogenesis imperfecta is also know as brittle bone disease.
  • It is a monogenic disorder, resulting from mutation in genes responsible for synthesis/function of type I collagen.
• Scurvy is a deficiency disease from a lack of vitamin C.
  • Inadequate vitamin C impairs proline and lysine hydroxylation, disrupting collagen synthesis.

Elastin

• Elastin is the primary component of elastic fibers as an insoluble protein.
• It contains nonpolar amino acids: glycine, alanine, valine, and lysine, plus desmosine and isodesmosine.
• Elastin resides in arteries, lungs, the bladder, skin, ligaments, and elastic cartilage.

Marfan Syndrome

• Marfan syndrome is a congenital condition.
• Its cause lies in mutations to the fibrillin 1 (FBN1) gene.
• The fibrillin 1 protein supports elastic fibers in connective tissue.

Muscle Contraction Proteins

• Sarcomeres contain thin (actin) and thick (myosin) filaments.
• Tropomyosin and troponin regulate actin.
• Myosin heads facilitate interactions.

Cytoskeleton

• The cytoskeleton defines the internal structural framework within eukaryotic cells.
• Proteins structure the complex components.

Proteins of the Cytoskeleton

• The cytoskeleton mainly supports the following functions:
  • Cell support via the internal components
  • Organized movement of intracellular components
  • Contributes to elasticity for cell structures
  • Enables cellular locomotion
  • Important during cell division.
• The 3 fundamental protein elements of the cytoskeleton: microfilaments, intermediate filaments, and microtubules.

Alpha-Keratin

• Alpha-keratin is a fibrous protein and functions as a part of intermediate filaments
• It is structured from coiled alpha helices, which adds the strength/rigidity to withstand mechanical stress.
• Alpha-keratin acts as a structural component in the skin, hair, nails, claws, feathers, beaks, scales, and hooves.
• Cysteine in alpha-keratin favors rigidity with disulfide bridges. Alpha-keratin can have hard or soft keratins based disulfide bond content.
• Flexible keratins are usually found in the skin where rigid are primarily in the nails or hair

Actina F - Microfilaments

• Responsible for contractile function in cell division and anchoring.
• Can function in ameboid-movement.

Tubulin - Microtubules

• Involved in intracellular transport, cell division, and forming cellular structures such as flagella and cilia.

Albumin

• Human serum albumin is a protein that gets produced in the liver.
• Albumin has tertiary structure, it has a key importance in biological functions that constitute 60% of the plasma proteins.
• Albumin retains oncontic blood pressure in the blood.
• Some transport capabilities of Albumin: drugs, bilirubin, fatty acids, steroid hormones, zinc, calcium.

Immunoglobulins

• Immunoglobulins also known as antibodies are proteins that get formed in the immune system as a response to antigens.
• It has a role in the body's defense against infections. It does this by specifically neutralizing/eliminating antigens.
• Immunoglobulins are formed in B lymphocyte cells.

Immunoglobulin Structure

• Contains 2 heavy chains (H) and 2 light chains (L) and a bisagra (hinge) region.
• Light chains are a variable portion (antigen connection site) and a constant portion (structural support)
• Heavy chains are a variable portion (antigen connection site) and a constant portion (structural support)

Types of Immonoglobulins

• IgG is the most frequent type. Protects against acquired immunity. Meaning, it can produce an immune response based on specific antigen.
• IgM is first response upon virus or antigen interaction. Also has complement system and important defense mechanism to fight.
• IgA is within mucosal linings to protect body surface, but also serves to neutralize toxins/pathogens.
• IgD is within the B lymphocytes. Plays role in lymphatic response.
• IgE allergic-reactions. Is caused by an immune response to an allergen where a production of IgE has inflammation to allergens with a excessive secretion.