SUBJECT

Molecular Biology - Selected Topics

lecture

master

Faculty of Science

Biology MSc

2

Semester 2

Spring semester

1. Protein folding in space and time. The thermodynamics of folding. Energetics - driving forces. Kinetics and dynamics. Mechanisms and topological considerations. Structure elements. Graphical visualization of protein structures.

2. Protein complexes in the energy production. The mechanism of bacteriorhodopsin. The proton pumping electron transport. ATP synthesis - the mechanism of the F1Fo ATP-ase. Photophosphorylation - the initial saving of light energy, the structure of photocenters.

3. Protein metabolism. The protein synthesizing RNA (ribozyme). Regualtion of translation - by attenuation. A helping hand chaperons and heat shock proteins - the structural basis of foldig catalysis. Protein targeting - across membranes. Protein degradation.

4. Several processes in nucleic acid metabolism. The mechanism of DNA repair by the Ku heterodimer. Mechanisms in changing the helicity of DNA. The nucleosomal packaging of DNA. The catalysits of DNA superspiralization. The initiation of RNA-dependent RNA plymerization. RNA synthesis. The mechanism of RNA editing. DNA transports - DNA pumping mechanisms.

5. The structure of biological membranes. Membrane lipids, types of membrane proteins, membrane anchors, complex carbohydrates: peptidoglycanes, proteoglycanes, glycoproteins, glycolipids, the membrane is more a mosaic than a fluid, membrane rafts.

6. The properties of biological membranes. Asymmetry, fluidity, pemeability, membrane potential. Membrane transpot processes: general features. Passive transports: aquaporin, GLUT, AE1. Active transport systems.

7. Transport ATP-ases: Na-K ATP-ase, Ca pumps, MDR, CFTR. Secunder active transport: E.coli lactose transporters, Na-glucose synporter. Ionophores. The structural basis of ionselectivity (KcsA, Na, Cl channels), gating mechanisms: voltage and ligand gating, membrane potential, excitatory and inhibitory signals.

8. Signa transduction I. General properties, investigation methods of ligand binding, cytoplasmic and nuclear receptors, NO, CO, and steroids. G-protein coupled mechanisms, characterization, the types, structures and functions of G-proteins, formation of second messengers (cAMP, IP3 and DAG), activation mechanisms of serine-theronine kinases, the role and regulation of the cytoplasmic Ca level during signal transduction. The Ca-binding proteins.

9. Signal transduction II. Enzyme-linked cell membrane receptors: receptor associated tyrosine kinases, hGH, hGHR, JAK, the functions and activation of the scr, the SH2 and SH3 domain-containing proteins (Grb-2, Sos), small G proteins. The receptor tyrosine kinases, NGFR, EGFR, signalling pathways of the insuline receptor, IRS-1 -> MAPK, PKB, receptor-like tyrosine phosphatases, receptor guanylyl cyclases. The molecular basis of vision, odor and taste perception.

10. The control of cell cycle. Phases of the cell cycle. Cell fusion experiments, the basic principles of the cell cycle. Model systems of the embryonic and somatic cell cycle, cdc mutants in yeast, the discovery of cyclins in oocytes. MPF, kinase-cyclin complex.

11. Fundamental components in the controll of cell cycle: point of competence and restriction, cycline-dependent kinases, cyclines, the regulation of cyclin-dependent kinases, phosphorylation, inhibition. Degradation of cyclines, exit from G0, cycline D, negative and positive feed- in G1, CDK-s in the S-phase, replication, the inhibition of reinitiation, regulation of the M- phase, check points in the cell cycle, the role of p53.

12. Apoptosis. Apoptosis vs necrosis, diseases and apoptosis, participating genes in apoptosis, the apoptotic genes of C. elegans, types of caspases, the ways of their activation, the substartes of caspases, the role of cytochrome c and other mitochondrial proteins in the apoptosis. The Bcl-2 family, death receptors, the role of p53 in the apoptosis.

13. The molecular biological basis of tumor formation. The gained functions of tumor cells: self signalling, loosing the apoptotic and gaining unlimited replicative potential, efficient angiogenesis, tissue penetration and metastases. The role of genetic ground, DNA repair processes.

14. Special processes - structural specialities. Molecular cold adaptation - biological antifreezers, molecular ice-breakers. The MHC molecule and its receptor. Mechanisms in viral infections.

• Lecture notes, slides on hand-outs,

• David Lee Nelson, Michael M. Cox: Biochemistry, 6th ed., W.H. Freeman, 2013

• Stryer, L. et al.: Biochemistry, W. H. Freeman, 2008