Learning outcomes of the course unit
The main objective of the course is to provide the student with the necessary tools for detailed and critical analysis of the structure of proteins and their macromolecular complexes. The first part of the course is dedicated to the understanding of the chemico-physical properties of the amino acids on which protein structure is based. Then the secondary and tertiary structures that constitute most proteins will be analysed in detail. The topics dealt with during the classroom lectures will be the subject of individual practical tests carried out in the computer science classroom where, with the use of dedicated software, students will attempt the structural analysis of biological macromolecules.
Course contents summary
* Physico-chemical properties of amino acids, the peptide bond, phi and psi angle of rotation, the Ramachandran diagram.
* Secondary structures: Alpha helixes, 3.10 and Greek pi, beta sheets, loop regions.
* Topological diagrams, calcium-binding helix-turn-helix motifs, beta hairpins, Greek a motif, beta-alpha-beta motif.
* Alpha helix structures: inter-helix contacts and superstructural organization of alpha-helix proteins, four helix bundle, globin folding.
* Alpha-beta structures: TIM barrel structure, Rossmann folding.
* Beta structure: "barrels" formed by antiparallel beta strands; Greek key motif; "jelly roll" (vitamin A-binding proteins; neuraminidase; gamma-crystallin; immunoglobulin and immunoglobulin-like proteins.
* Proteins with enzyme activity: serin protease, enzyme-substrate complex, Km, Kcat, Vmax, the transition state, mechanism of action of chimotrypsin, specificity, convergent evolution.
* DNA structure.
* DNA recognition by prokaryotic transcription factors: the helix-turn-helix motif, specific and non-specific interactions, Cro, lambda repressor, Lac operon repressor, CAP, tryptophan repressor, allosteric effectors that alter the affinity of protein for DNA.
* DNA recognition by eukaryotic transcription factors: TBP, specific sequence interactions, hydrophobics and plasticity of DNA, homeodomain proteins, POU regions. Zinc finger motifs, GCN4 leucin zipper.
* Membrane proteins: bacteriorodopsin, porines, potassium channel, hydropathy graphs, Cys-loop receptors.
* Protein folding: conformational flexibility, thermodynamic and kinetic factors that affect folding, isomerization of proline residues, structure and function of GroEL/GroES chaperonines.
* Quaternary structures.
* Notes on the determination of protein structure by means of X rays.
Branden C., Tooze J.
INTRODUZIONE ALLA STRUTTURA DELLE PROTEINE (II Edizione)
Zanichelli Editore, 2001
General supporting texts:
Nelson D.L., Cox M.M.
I PRINCIPI DI BIOCH IMICA DI LEHNINGER (III Edizione)
Zanichelli Editore, 2002
Specialist texts and other supporting material available for consultation:
Lesk A. M.
Oxford University Press, 2001
Petsko G.A., Ringe D.
PROTEIN STRUCTURE AND FUNCTION
New Science Press Ltd, 2002
In addition to the classroom lectures, the course includes 16 hours in the computer science classroom where the student will attempt the structural analysis of proteins through the use of RASMOL. The examination consists of a written test and an oral paper regarding the structural description of the assigned protein.