Introductory description

LF244 introduces students to the beauty and complexity of protein structures and the remarkable diversity of their biological functions. The course explores topics such as protein folding, DNA binding, electron transfer, protein engineering and membrane proteins. Students will also learn how to view and analyse protein structures with computational tools.

Module aims

Outline syllabus

This is an indicative module outline only to give an indication of the sort of topics that may be covered. Actual sessions held may differ.

1. The basic facts and principles.
   The importance of proteins as the executive agents of genes; protein structure as polymers of amino acids; representations of protein structures to show end results of protein folding and the dimensions involved.

2. Amino acids.
   Structure and properties of the 20 protein amino acids, including dissociation of charged groups, the hydrophobic interaction and the importance of side chain variation for the properties of proteins.

3. Peptide bonds and secondary structure.
   Amino acids chirality and planarity; phi and psi angles, Ramachandran plot, alpha helices, beta sheets. Loops.

4. Protein motifs, domains and beyond.
   Secondary structure elements in proteins and the forces that drive proteins to fold. Regular structures in proteins; secondary structures; the alpha helix and beta strand and their characteristics, loops and their importance. Protein super secondary structures; motifs and super secondary structures; domains built from structural motifs. Alpha, alpha/beta and beta structures.

5. Protein engineering.
   Why engineer proteins? Rational design of proteins for study and application. Site directed mutagenesis, Fusion proteins, Directed evolution, Lysozyme heat stability by addition of cysteines for disulphide bond thermostability of lysozyme; Noble prize 2018. Self study requirements.

6. Protein engineering: Lecture content on Green and other colours florescent proteins, Phage display to humanised antibodies.

7. Protein Folding - Part I.
   Properties of the folded and unfolded states; Levinthal's paradox; Folding landscapes.

8. Protein Folding - Part II.
   Anfinsen's Dogma; Predicting structure from sequence.

9. Chaperones.
   How do chaperones assist folding? The Anfinsen Cage mechanism; Iterative annealing mechanism.

10. DNA binding proteins.
    How do proteins recognise DNA? Sequence recognition in the DNA minor and major groove; Specific and non specific binding; Engineered DNA binding proteins (zinc fingers and Tal effectors)

11. Electron transfer proteins.
    Redox centres; Molecular wires; thiol-disulfiude interchange

12. Structure and mechanism of the SARS CoV 2 Spike protein.
    Structure of the coronavirus spike; Receptor recognition (protein-protein interaction); membrane fusion (protein conformational change).

13. Membrane proteins.
    Transmembrane helices; Beta barrels; Membrane protein functions.

14. Membrane protein insertion and transport.
    Assembling/inserting membrane proteins (SEC); Membrane proteins in the bacterial outer membrane (BAM)

In silico practical
Use of computational tools for viewing and analysing 3D protein structures.
Analysing nucleotide sequences. Linking genetic mutation to protein structure and function.

Learning outcomes

By the end of the module, students should be able to:

• Discuss the relationship between a protein's structural features and its function.
• Discuss molecular mechanisms with reference to a protein's 3D structure.
• Discuss the forces that drive protein folding.
• Apply knowledge of secondary structure elements, ligands and motifs to identify and describe protein structures.
• Assess and evaluate recent advances in protein structure prediction.
• Use molecular visualisation software to inspect and analyse 3D protein structures and create structural images.

Subject specific skills

Knowledge of protein structure and function.
Use of computational tools for visualising proteins.
Use of bioinformatics programmes for nucleotide sequence analysis
Producing scientific figures.

Transferable skills

Self-directed learning.
Computer skills.