神经科：蛋白质与疾病.pptxVIP

蛋白质与疾病May 19th, 2015 Protein related diseasesNat Rev Neurosci 2003, 4:49-60 Protein Structure is Hierarchical Protein Structure is Hierarchical Structure Determines Function Primary Structure: SequenceThe primary structure of a protein is the amino acid sequence Primary Structure: SequenceTwenty different amino acids have distinct shapes and properties Secondary Structure: ?, ?, loops? helices and ? sheets are stabilized by hydrogen bonds between backbone oxygen and hydrogen atoms Secondary Structure: ? helix Secondary Structure: ? sheetb sheetb buldge Tertiary Structure: Domains Tertiary Structure: A Protein Fold Three Dimensional Structure of Proteins Quaternary Structure: Multimeric Proteins or Functional AssembliesMultimeric ProteinsMacromolecular AssembliesRibosome:Protein SynthesisReplisome:DNA copyingHemoglobin:A tetramer Protein FoldingThe process by which a protein acquires its native tridimensional structure. Under physiological conditions, each protein has a unique stable folded structure, but in conformational disorders the polypeptide chain adopts an alternative structure, associated with the pathogenesis of the disease. Regulation of Protein Folding in the ERMany newly synthesized proteins are translocated into the ER, where they fold into their three-dimensional structures with the help of a series of molecular chaperones and folding catalysts (not shown). Correctly folded proteins are then transported to the Golgi complex and then delivered to the extracellular environment. However, incorrectly folded proteins are detected by a quality-control mechanism and sent along another pathway (the unfolded protein response) in which they are ubiquitinated and then degraded in the cytoplasm by proteasomes.Nature 2003, 426: 884-890 Molecular ChaperonsHeat shock protein (Hsp)/热休克蛋白: HSP40、HSP70Chaperonins/伴侣素 GroEL、GroESFoldase/折叠酶 Protein disulfide isomerase (PDI)、Peptidyl prolyl cis/trans isomerase (PPI) HSPs in Protein Folding The diagram