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Claire Lesieur Nucleus Protein Lipids Chromosome DNA Nucleus(chromosome) Membrane (Lipids) Proteins CHON.

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Presentation on theme: "Claire Lesieur Nucleus Protein Lipids Chromosome DNA Nucleus(chromosome) Membrane (Lipids) Proteins CHON."— Presentation transcript:

1 Claire Lesieur

2 Nucleus Protein Lipids Chromosome DNA Nucleus(chromosome) Membrane (Lipids) Proteins CHON

3 - Cutting - Recognition - Enzyme - Signaling - Carrier - Shape generator - Road networks



6 Function Shape How the shape provides a particular function How the shape is acquired


8 How it folds: Mechanisms of protein folding How the information is encrypted in the sequences: CODING problem ADRTGGILLKMHGGARECVVP

9 All the information necessary for the protein folding is within the protein primary sequence C.B. Anfinsen, Haber, E., Sela, M. & White, F. H., Proc. Nati. Acad. Sci. USA 47 (1961) Levinthals paradox(1968): not random search but directed Levinthal, C. (1968) J. Chim. Phys. 65,

10 Short range interaction Structure Tertiaire COOH H2NH2NH2NH2N ms s-hours Structure primaire Structure Secondaire long-rangeinteractions short-rangeinteractions

11 X-ray crystallography + NMR: PDB 3D modeling: PDB ~ 70 % Sequence similarity: 3D modeling 70 % similarity: different shape Low sequence similarity: similar shape Amino acids on the surface of proteins: changeable

12 -strands transmembrane domain: strands transmembrane domain: helice transmembrane domain: helice transmembrane domain:


14 Geometrical constrain Chemical constrain

15 Domains Shape and role ?? Sequence Pattern


17 Trends in Microbiology (2000). Vol 8 (4):

18 Cholera toxin AB 5 toxinAB 5 toxin –A catalytic subunit –B receptor binding subunit GM 1 : cell receptorGM 1 : cell receptor Endocytosed and traffic to the EREndocytosed and traffic to the ER ADP ribosylation of G subunitADP ribosylation of G subunit Increase of cAMP leading to water lossIncrease of cAMP leading to water loss CtxB 5 CtxA ER


20 Assembly in vitro PentamereMonomere pH 1 15 min pH 7


22 Trp-fluorescence Fluorescence Intensity unfolded Wavelength (nm) Time (min) ex = 295 nm ex = 295 nm em =352 nm em =352 nm Fluorescence Intensity (a.u.)

23 His ,555,566,577,58 pH CtxB Function HISTIDINE

24 … … CtxB5


26 Heat labile enterotoxin B Cholera toxin B LTBCtxB

27 N-terminal ,555,566,577,58 pH LTBCtxB Function N-terminal

28 LTB5

29 Kinetics differences On pathway intermediates differences It is particular amino acids that are responsible for each individual step of assembly and folding

30 Alzheimer, Parkinson, Prion diseases Protein X: FOLD state: healthy (Protein X)n: Assembly state: Lethal Information for interfaces

31 Protein Interface formation Rules? Mechanism? Preferential geometries related to preferential sequences of amino acids?

32 INTERFACES: Zone de contact entre monomeres voisins

33 InterfaceTrimer pentamerheptamer Brin 1 Brin C h 111C h n.a. C h 111C h 1111/1


35 Fibritin like domain

36 Nombre de monomer Nombre de cas

37 LMITTECMVTDL aaa-bbbbbbb GRNVVLDKSFGAPTI --bbbb bb Monomer M Monomer M+ 1 Distances



40 3BDU 20-29, 38-53


42 1LEP: 1-8, 88-94, WNR: 1-8, 88-94, 44-57, HX5: 5-11, 94-97, 51-62, 68-80, G31: 8-15, , 68-85


44 yeast P. aerophilum: bacterium Methanobacterium Thermautriophicum: extremophile 1N9R 1LNX 1JBM

45 1JBM: 12-18, 42-50, LNX: 10-15, 25-32, 40-48, N9R: yeast P. Aerophilum Hyperthermophilic bacterium Methanobacterium Thermautriophicum: extremophile


47 2CBY

48 Geometry and function related Family of protein interfaces Assembly keys

49 Classification of protein interfaces: Database Systematic analysis of protein interfaces- subjective classification Mathematical approach: Laurent Vuillon (LAMA) Functional analysis of protein interfaces Protein Assembly mechanism from block: Giovanni Feverati Stoechiometry/Symmetry: Paul Sorba Experimental tests: Claire Lesieur

50 Alicia Ng Ling Mun Keat Chong Boon Leng Chua Danyang Kong Giovanni Feverati Paul Sorba

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