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Mednarodna
podiplomska šola
Jožefa Stefana

Jamova 39
SI-1000 Ljubljana
Slovenija

Tel: (01) 477 31 00
Faks: (01) 477 31 10
E-pošta: info@mps.si

Išči

Opis predmeta

Stabilnost, zvijanje in agregacija proteinov

Programi:

Nanoznanosti in nanotehnologije, 3. stopnja

Sodelavci:

prof. dr. Eva Žerovnik

Cilji:

Študentje spoznajo osnove zvijanja proteinov in njihove stabilnosti. Pridobijo vpogled v termodinamske, kinetične in strukturne vidike procesa zvijanja. Nadalje se seznanijo s povezanim mehanizmom agregacije proteinov. Ta se pojavlja pri nevrodegenerativnih boleznih.

Vsebina:

Študij zajema naslednje teme:
• Stabilnost proteinov: osnovna znanja o določanju stabilnosti
• Problem zvijanja proteinov – kako se proteini zvijajo in vitro in in vivo
• Kinetika, prehodna stanja in energije prehodov (energijske površine)
• Kako se zvijanje začne – najzgodnejše stopnje
• Razrahljani klopčič (molten globule) – pomen za zvijanje, npačno zvijanje in prehajanje preko membrane
• Termodinamika ne zadostuje
• Vloga šaperonov kot katalizatorjev
• Agregacija proteinov do amiloidnih fibril: in vitro in v celici
• Zvijanje proteinov in bolezni: nevrodegenerativne bolezni

Temeljna literatura in viri:

Book: Mechanisms of Protein Folding, 2nd edn., (2000) R. H. Pain (ed.), Oxford University Press.

Additional book: Protein Folding-Misfolding: some current concepts of protein chemistry. Zbilut JP and Scheibel T (eds.), Nova Sci Publi., New York, 2007.

Additional book: Protein misfolding diseases; current and emerging therapies. eds Raminez-Alvarado, J.W. Kelly, C.M. Dobson, Wiley Series in Protein and Peptide Science, Series Ed. V.N. Uversky. John Wiley & Sons, New Jersey 2010.

Special issue of Current Opinion in Structural Biology vol 18, pp. 1- 130, 2008. Folding and Binding Itzhaki L and Wolynes P (eds.)

Selected papers:

Eichner T, Kalverda AP,. Thompson GS, Homans SW. and Radford SE (2011) Conformational Conversion during Amyloid Formation at Atomic Resolution. Molecular Cell 41: 161–172.

Sharma, S. et al. (2008). Monitoring protein conformation along the pathway of chaperone-assisted folding. Cell, 133,142-153.

Felitsky et al., (2008). Modeling transient collapsed states of an unfolded protein to provide insights into early folding events. Proc. Natl. Acad. Sci USA 105: 6278-6283.

Schuler and Eaton (2008). Protein folding studied by single-molecule FRET. Curr Opin. Struct. Biol.18: 16-26.

Ohnishi S and Takano K (2004): Amyloid fibrils from the viewpoint of protein folding. Cell Mol Life Sci. 61: 511-524.

Review papers:

Lashuel HA, Lansbury PT Jr. (2006) Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins? Q Rev Biophys. 39, 167-201.

Izbrane reference nosilca:

Jelinska C, Davis PJ, Kenig M, et al. (2011) Modulation of Contact Order Effects in the Two-State Folding of Stefins A and B. Biophys.J. 100: 2268-2274.

Taler-Vercic A, Zerovnik E (2010) Binding of amyloid peptides to domain-swapped dimers of other amyloid-forming proteins may prevent their neurotoxicity. BIOESSAYS 32 : 1020-1024.

Škerget K, Taler-Verčič A, Bavdek A, et al. (2010) Interaction between Oligomers of Stefin B and Amyloid-beta in Vitro and in Cells J.Biol.Chem. 285: 3201-3210.

Morgan GJ, Giannini S, Hounslow AM, et al. (2008) Exclusion of the native alpha-helix from the amyloid fibrils of a mixed alpha/beta protein. J. Mol. Biol. 375: 487-498

Čeru, S and Žerovnik, E. (2008) Similar toxicity of the oligomeric molten globule state and the prefibrillar oligomers. FEBS lett. 582, 203-209.

Jenko Kokalj S, Guncar G, Stern I, et al. (2007) Essential role of proline isomerization in stefin B tetramer formation. J.Mol.Biol. 366: 1569-1579.

Lejeune A, Pain RH, Charlier P, Frčre JM, Matagne A. (2008): TEM-1 beta-lactamase folds in a non-hierarchical manner with transient non-native interactions involving the C-terminal region. Biochemistry47:1186 93

Kenig, M, Jenko-Kokalj, S, Tušek-Žnidarič, M, Pompe-Novak, M, Gunčar G, Turk D, Waltho JP, Staniforth, RA, Avbelj, F and Žerovnik, E (2006) Folding and amyloid-fibril formation for a series of human stefins' chimeras: Any correlation? Proteins 62, 918-927.

Staniforth RA, Dean JL, Zhong Q, Žerovnik E, Clarke AR, Waltho JP. (2000). The major transition state in folding need not involve the immobilization of side chains. Proc Natl Acad Sci U S A. 97, 5790-5795.

Jerala, R and Žerovnik, E. (1999) Accessing the global minimum conformation of stefin A dimer by annealing under partially denaturing conditions. J. mol. biol. 291, 1079-1089.

Žerovnik, E, Virden, R, Jerala, R, Kroon-Žitko L, Turk, V and Waltho, JP. (1999). Difference in the effects of TFE on the folding pathways of human stefins A and B. Proteins 36, 205-216.

Wheeler, K. A., Hawkins, A. R., Pain, R. H. and Virden, R. (1998): The slow step of folding of Staphylococcus aureus -lactamase involves the collapse of a surface loop rate limited by the trans to cis isomerization of a non-prolyl peptide bond. Proteins: Structure, Function and Genetics 33, 550-557.

Žerovnik, E., Jerala, R., Kroon-Žitko, L., Pain, R.H. and Turk, V. (1992). Intermediates in denaturation of a small globular protein, recombinant human stefin B. J. Biol. Chem. 267, 9041- 9046.

Ptitsyn, OB, Pain RH, Semisotnov GV, Žerovnik, E and Razgulyaev OI .Evidence for a molten globule state as a general intermediate in protein folding. FEBS lett. 262, 20-24 (1990).

Načini preverjanja znanja:

• ustno preverjanje

Obveznosti študentov:

• sprotne naloge, ustni izpit

Zunanje povezave: