How it folds: Mechanisms of protein folding How the information is encrypted in the sequences: CODING problem ADRTGGILLKMHGGARECVVP
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) 1309-1314. Levinthals paradox(1968): not random search but directed Levinthal, C. (1968) J. Chim. Phys. 65, 44-45.
Short range interaction Structure Tertiaire COOH H2NH2NH2NH2N ms s-hours Structure primaire Structure Secondaire long-rangeinteractions short-rangeinteractions
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
Trends in Microbiology (2000). Vol 8 (4):169-172
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
Geometry and function related Family of protein interfaces Assembly keys
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
Alicia Ng Ling Mun Keat Chong Boon Leng Chua Danyang Kong Giovanni Feverati Paul Sorba
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