Learning objectives
The main objective of the course is to provide students with the tools needed for detailed and critique analysis of the protein structure their macromolecular complexes. The first part of the course is dedicated to the understanding of the physico-chemical properties of amino acids that are the basis of protein structure. Subsequently we will analyze the details of secondary and tertiary structures found in the majority of proteins. Topics covered during the lectures will be hands-on in a computer room where, with the use of software, students will engage with the structural analysis of biological macromolecules.
Course unit content
* Physico-chemical properties of amino acids, the peptide bond, phi and psi angle of rotation, the Ramachandran diagram.
* Protein synthesis
* 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 ion channels.
* F1F0 ATPase structure
* Protein folding: conformational flexibility, thermodynamic and kinetic factors that affect folding, isomerization of proline residues, structure and function of GroEL/GroES chaperonines.
* Fibrous proteins: alpha cheratines, collagen, fibroin.
* Methods for the determination of protein structure.
Bibliography
Branden C., Tooze J. INTRODUZIONE ALLA STRUTTURA DELLE PROTEINE (Zanichelli, II Ed., 2001)
Petsko, G.A., Ringe D., STRUTTURA E FUNZIONE DELLE PROTEINE (Zanichelli, 2006).
Nelson D.L., Cox M.M. I PRINCIPI DI BIOCHIMICA DI LEHNINGER (Zanichelli, III ed., 2002)
David Whitford, PROTEINS STRUCTURE AND FUNCTION (Wiley)
http://books.google.it/books?id=qbHLkxbXY4YC
