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Proposal • • • • Abstract/Specific Aims (1 page) Background (4-6 pages) Research Plan (8-10 pages) References • Proteins • Protein Structures and Shapes • Protein Functions Protein Structures and Shapes • Amino acids • Peptide bonds a helix and b sheet • Domains and Modules • Classification of Families • Protein Assembly Protein Functions • • • • • • • • • Protein Binding Protein conformation Antibody Enzyme and substrate Catalytic Reaction Kinase and phosphatase GTPase, GEF, GAP Motor protein Membrane-bound protein Protein binding Antibody Enzymes lower the activation energy to accelerate chemical reactions Lysozyme actions Bending of the polysaccharide bond Steps of lysozyme actions Strategies of enzyme catalysis Feedback inhibitions Coupled regulation: Positive Regulations Coupled regulation: negative Regulations Coupled regulation on multiple subunits Aspartate transcarbamoylase Kinase and phosphatase Kinase Domain Kinase families Cyclin-dependent Kinase (CdK): Signal integrator threonine tyrosine Src Kinase Multiple Inputs for Src Kinase activation GTPases Ras Structure: One kind of GTPases Phosphorylation and GTP binding regulations EF-Tu and its regulation of tRNA Motor Protein Regulation Myosin on Actin and Kenesin on Microtubules Membrane Protein Calcium Pump on Sarcoplasmic reticulum • DNA and Chromosomes Chromosome in Cells DNA (deoxyribonucleic acid) AGTC Human 46 chromosomes 22 homologs, x, or x/y Experimental procedures demonstrating that DNA is the genetic material DNA and its Building DNA and its Building DNA Pairs A-T, G-C DNA Double Helix 10.4 nucleutides/turn; 3.4 nm between nucleutides DNA to Protein genome DNA Duplication Using itself as template Cell Nucleus Human Chromosome Complementary DNA with different Dyes The arrangement of the full chromosome set is called karyotype Banding Pattern of human chromosomes Giemsa Staining Encoding ribosome The organization of genes of a human chromosome Conservation between human and mouse genomes human mouse centromere Cell Cycle Chromosomes exist through the cycle Chromosomes at interphase and M phase Three DNA sequences Nucleosomes under electron microscope Nucleosome: basic level of chromosome/chromatin organization Chromatin: protein-DNA complex Histone: DNA binding protein Nucleosome Structures Histone octamer 2 H2A 2 H2B 2 H3 2 H4 X-ray diffraction analyses of crystals Structural Organization of the Core Histones The Assembly of the Core Histones The bending of DNA in a nucleosome A-T riched minor groove inside and G-C riched groove outside Zigzag model of the 30-nm chromatin fiber Irregularities in the 30-nm fiber Flexible linker, DNA binding proteins The function of Histone H1 The function of Histone tails Chromatin Remodeling Cyclic Diagram for nucleosome formation and disruption Covalent Modification of core histone tails Histone acetyl transferase (HAT) Histone deacetylase (HDAC)