7-9 Protein

Composition of Milk:
- Composed of various proteins, particularly casein (approximately 80% of milk protein).
- Types of casein include:
  - Alpha casein
  - Beta casein
  - Kappa casein
- Contains 0.7-0.9% phosphate by weight.
- Remaining 20% includes whey proteins:
- Lactoglobulin
- Lactalbumin
Techniques for Protein Analysis:
- Use of MALDI-TOF mass spectrometry to separate proteins based on mass-to-charge ratio.

Protein Presence in Cells:
- Proteins represent 55-60% of the cell’s dry weight in certain cells.
Definition of Proteins:
- Proteins are polymers of amino acids linked via peptide bonds.
- Origin of the term: From Greek “proteios,” meaning primary.
Functions:
- Proteins facilitate crucial biological processes. Their diverse functions stem from:
- Thousands of unique proteins, each with a distinct three-dimensional structure that allows interaction with various molecules.
- Abnormal structures may result in molecular diseases affecting metabolic functions.
Proteome Definition:
- The complete set of proteins expressed by a genome within a biological context.
Genomic Information:
- Representation of the genome via DNA sequencing:
- Caenorhabditis elegans genome: 97 million bases, 19,000 protein-encoding genes.
- Drosophila melanogaster genome: 180 million bases, approximately 14,000 genes.
- Human genome: 3 billion bases with about 23,000 protein-coding genes.
Dynamic Nature of Proteomes:
- The proteome varies by cell type, developmental stage, and environmental conditions.
- Proteomics is the study of protein analysis.

Functionality:
- Protein engineering aims to define structure–function relationships through the creation of mutant proteins.
- Involves genetic engineering, expression, purification, and analysis of wild-type and mutant proteins.
Applications:
- Creation of enzymes, peptide hormones, and antibodies optimized for specific purposes.

Diverse Functions of Proteins:
- Functions span multiple applications in clinical and industrial fields, for example,:
1. Catalysis: Enzymes facilitate biochemical reactions.| Example: RuBisCO in photosynthesis, Nitrogenase for nitrogen fixation.
2. Structural Support: Proteins like collagen and elastin provide mechanical strength.
3. Movement: Cytoskeletal proteins (actin and tubulin) promote cellular motion.
4. Defense: Protective proteins (keratin, immunoglobulins) defend against injury and pathogens.
5. Regulation: Hormones (insulin and glucagon) regulate physiological processes.
6. Transport: Hemoglobin transports oxygen; Na+ -K+ ATPase aids in membrane transport.
7. Storage: Proteins provide a nutrient reservoir (e.g., ovalbumin, casein).
8. Stress Response: Heat shock proteins help in protein refolding and destruction of damaged proteins (e.g., cytochrome P450).
9. Toxins: Neurotoxins assist in predation (e.g., snake venoms).
10. Gene Regulation: Proteins like RNA polymerases and DNA ligases are vital for transcription and replication.
11. Multifunctional Proteins: Some proteins serve multiple roles (known as moonlighting proteins).
12. Miscellaneous Functions: Antifreeze proteins found in cold-resistant fish, and Green fluorescent proteins (GFP) used in research for gene expression and localization studies.

Formation of Peptide Bonds:
- Two amino acids link through a peptide bond during a dehydration reaction, forming a dipeptide.
- Reaction occurs at the ribosomal peptidyl transferase center, crucial in protein synthesis.
Structure and Stability:
- Peptide bonds demonstrate directional properties; standard sequence naming from the amino-terminal to carboxyl-terminal end.
- Different lengths:
- 2 amino acids: dipeptide
- 3 amino acids: tripeptide
- 4 amino acids: tetrapeptide
- 10 to 50 amino acids: polypeptide
- Over 50 amino acids: classified as proteins.
- Peptide bonds are highly stable with an average half-life of approximately 7 years under physiological conditions.
Characteristics of Peptide Bonds:
- Exhibit partial double bond character due to resonance contributing to planar structure.
- Predominantly exist in trans configuration, allowing proteins to form globular structures.

Explanation of Isopeptide Bonds:
- A type of amide bond distinct from the peptide bond, formed via covalent attachment during ubiquitin-protein interactions.
Example:
- Glutathione features an unusual γ-amide bond, critical in cellular detoxification processes.

Definition: The amino acid sequence of a polypeptide chain; specified by genetic coding, e.g., alpha endorphin: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr.

Characteristics: Regular folding of polypeptide chains; includes:
- Alpha helix: Stabilized by hydrogen bonds; pitch length approximately 0.54 nm with a right-handed twist; 3.6 amino acids per turn.
- Beta-sheet: Composed of beta strands linked by hydrogen bonds, capable of parallel or antiparallel arrangements.
- β-turn: A common structural element allowing 180° turns in the polypeptide chain, facilitates compact structures in proteins.

Defines the overall three-dimensional conformation of a protein maintained by:
- Covalent disulfide bonds and noncovalent interactions (hydrogen bonds, ionic bonds, van der Waals forces).

Arrangement of multiple polypeptide chains (subunits); may exhibit identical subunits (oligomeric) or different compositions.
Example: Hemoglobin consists of four polypeptide chains, demonstrating complex quaternary arrangement.

Molecular Chaperones: Assist in the correct folding of proteins post-translation.
- Hsp70 Family: Binds to hydrophobic regions to prevent misfolding; utilizes ATP hydrolysis.
- Hsp60 Family (Chaperonins): Forms isolation chambers for protein folding, ensuring proper conformation away from aggregation.
Protein Quality Control: Systems regulate folding, recognize misfolded proteins, and orchestrate refolding or degradation pathways to maintain cellular integrity.

Protein Turnover Definition: The balance of protein synthesis and degradation.
Degradation Mechanisms:
- Ubiquitin-proteasomal degradation pathway primarily tags misfolded or short-lived proteins.
- Autophagy involves lysosomal degradation ensuring cell component recycling and homeostasis.
Ubiquitin Tags: Signal for proteins destined for degradation; specific sequence motifs (degrons) dictate degradation speed.

Diseases are often characterized by amyloid fibrils resulting from misfolded proteins:
- Alzheimer's Disease: Amyloid-beta peptide formation.
- Huntington's Disease: Accumulation of huntingtin protein.
- Parkinson's Disease: Alpha-synuclein aggregation.
Amyloid Formation Mechanism: Involves protein misfolding and aggregation processes that lead to disease pathology, influencing cellular functioning adversely.