Biochemistry - Protein Function Overview

Biochemistry - Protein Function

• Learning Outcomes:
  • Understand the link between DNA, mRNA, and proteins.
  • Understand the link between protein sequence, structure, and function.
  • Be aware of the importance of protein bioinformatics in modern biology and how molecular evolution informs protein biology.

DNA - The Carrier of Genetic Information

• Central Dogma of Modern Biology:

  • DNA replicates itself, providing information for protein building.
  • Transcription: DNA information is passed to RNA for protein building.
  • Translation: RNA carries the code to make proteins.

• DNA carrying genetic information:

  • Gene: The unit of inheritance.
  • ~20,000 protein-encoding genes in the human genome (approximately 3,000,000,000 base pairs). The stretches of DNA surrounding genes are called flanking regions.
  • Structural RNA molecules (e.g., rRNA, tRNA) are part of the genetic information.
  • A gene is a sequence of DNA bases.
  • RNA polymerase binds to a promoter and copies DNA to create mRNA.

• Genetic Code:

  • mRNA binds to a ribosome and is translated into an amino acid sequence.
  • The genetic code determines which amino acid corresponds to each triplet of mRNA bases. Examples of codons are AUG (Methionine) and GGG (Glycine). There are also stop codons like UGA.

Proteins - The Machinery of Life

• Functions of Proteins: Enzymes, hormones (e.g., insulin), membrane channels/transporters (e.g., aquaporin, Na+/K+ channels), membrane receptors (e.g., GPCRs, 50% of drug targets), transport (e.g., hemoglobin), signaling molecules (e.g., cytokines), gene regulation, movement (e.g., actin, myosin), contribute to the structure of cells/tissues (e.g., collagen)

Haemoglobin (Hb)

• Oxygen Transport:
  • Oxygen (O₂) is hydrophobic.
  • Haemoglobin (Hb) is found in red blood cells (RBC) and transports oxygen from the lungs to the tissues.
  • Hb has two α-chains and two β-chains.
  • Hb contains a haem group which binds oxygen (O₂) via an iron ion (Fe²⁺).

Protein Bioinformatics

• Purpose:

  • Sequence analysis (pairwise or multiple sequence alignments).
  • Identify key amino acids (e.g., active site amino acids in enzymes).
  • Identify and determine protein function.
  • Predict protein structure.

• Types of protein sequences:

  • Homologous sequences: Two or more proteins derived from a common ancestor through divergent evolution. Examples include human and sperm whale myoglobin (despite different species, the protein structure is largely the same). This is also true for different types of myoglobin and haemoglobin within the same species

• Multiple Sequence Alignment:

  • Highlights regions of similarity and functionally/structurally important amino acid patterns (motifs) within amino acid sequences. Tools like Clustal are used to do this.
  • Studying the conserved amino acids, like the two His amino acids in haemoglobin, is crucial to understanding the protein's function.

• Importance of 3D Structure: Correct 3D structure is vital for proteins' biological activity.