KHW BMElectureNov10 - Protein Overview ! Biological...

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Protein Katherine Henzler-Wildman, Biochemistry & Molecular Biophysics Overview Biological Importance of Proteins Methods of Protein Structure Determination Protein Structure: What proteins look like – How we think about protein structure at all levels – Different ways of showing the features of protein structure Protein dynamics: The importance of motion in protein function – How can we measure dynamics – Three examples: myoglobin, adenylate kinase, membrane transporters Biological Importance of Proteins Why do we care about proteins? What Do Proteins Do? Catalysis (Enzymes) The machines of the cell Perform chemical reactions to break down old molecules and build up new ones Contractile Proteins and Motors Move things within cell Change cell shape Move cell around (cilia, flagella) Transport Move molecules across membranes Move molecules within and between cells Storage/Nutrient Proteins HIV Protease
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What Do Proteins Do? • Regulation and Signaling (Receptors, Kinases) Receive signals and pass them along appropriately Sense conditions within and around cell Communication between cells, within the cell Control gene expression Control function of other proteins Defense (Antibodies, Toxins) Recognize invaders Kill invaders Structural Form skeleton of cell Form strong or protective structures (silk, fingernails, etc.) F-actin Basic Protein Requirements Binding – Small molecules – Other proteins – Nucleotides – Lipids Catalysis – Chemical reactions to break down things that aren’t needed and build up things that are needed Conformational stability – Structural integrity – Scaffold for functionally important features Conformational change (dynamics) – Movement needed to perform functions as cellular machines, motors, transporters, regulators TATA Binding Protein Our current understanding: Genes Protein Sequence Protein Structure Protein Dynamics Protein Function Protein Structure Determination Methods How do we figure out what a protein looks like when it’s too small to see, even under a microscope?
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X-ray crystallography Strelov, et al., Crystal ography Reports 53: 143-146 (2008) http://lysozyme.co.uk/crystal ization.php 1. Grow crystals - Well-ordered array of protein molecules so that light scatters off all the molecules in the same way - Trial and error to find crystallization conditions 2. Collect diffraction pattern 3. Solve structure! h ! X-ray crystallography PDB: 1HEL: lysozyme at 1.7Å resolution http://www.synchrotron-soleil.fr/portal/page/portal/Soleil/ ToutesActualites/2008/SimulationMoleculaire The protein molecules are packed into a well-ordered repeating array in the crystal Resolution matters! X-ray crystallography
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KHW BMElectureNov10 - Protein Overview ! Biological...

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