proteins ccc 21_08_2012 modified

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  • Lecture 1 CCC -Proteins........ Modified lecture presentations will also be posted after thelecture; and may include additional materials, includingproblem sets any . 1
  • Proteins:Make up about 15% of the cellHave many functions in the cellEnzymesStructuralTransportMotorStorageSignalingReceptorsGene regulationSpecial functions 2
  • Primary structure = order of amino acids in the protein chain 4
  • Anatomy of an amino acid 5
  • Non-polar (Hydrophobic) a.a 6
  • Polar, non-charged amino acids 7
  • Negatively-charged amino acids 8
  • Positively-charged amino acids 9
  • Charged/polar R-groups generally map to surfaces on soluble proteins 10
  • Peptide Bonds- -carboxyl of one amino acid is joined to -amino of a second amino acid (with removal of water)- only -carboxyl and -amino groups are used, not R-group carboxyl or amino groups 11
  • peptide bond formation 12
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  • The peptide bond is planar 14
  • Peptide bonds is planar and quite rigid.Therefore the polypeptide chain has rotational freedom only aboutbonds formed by alpha carbons.These bonds have been termed as Phi (alpha C N) andPsi angle (alpha C-C).However the rotational freedom about these abgles is limitedby steric hindrance between the side chains of the residues and thepeptide bachbone. 15
  • Primary sequence reveals important clues about a protein Evolution conserves amino acids that are important to proteinstructure and function across species. Sequence comparisonof multiple homologs of a particular protein reveals highlyconserved regions that are important for function. Clusters of conserved residues are called motifs -- motifscarry out a particular function or form a particular structure thatis important for the conserved protein. motif DnaG hydrophobic small E. coli ...EPNRLLVVEGYMDVVAL... DnaG hydrophobic large S. typ ...EPQRLLVVEGYMDVVAL... DnaG B. subt polar ...KQERAVLFEGFADVYTA... gp4 positive T3 charge ...GGKKIVVTEGEIDMLTV... gp4 negativeT7charge ...GGKKIVVTEGEIDALTV... : : : : * * 16 : : *
  • Secondary structure = local folding of residues into regular patterns or local conformation of the polypetide chain independent of the rest of the protein 17
  • Alpha helix and Beta sheets were actually predicted byLinus Pauling, Robert Corey and H R Branson in 1951.Alpha helix and Beta sheets are the regular secondary structures.-helix can be coiled in two directions, Left or right . Almost all helicesObserved in proteins are Right Handed, as steric hinderance limit theability of left handed helices to form.Among the right handed helices the -helix is most prevalent.-helix= 3.6 resideus per turn of the backbone coil. 18
  • The -helix In the -helix, the carbonyl oxygen of residue i forms a hydrogen bond with the amide of residue i+4. Although each hydrogen bond is relatively weak in isolation, the sum of the hydrogen bonds in a helix makes it quite stable. The propensity of a peptide for forming an -helix also depends on its sequence. 19
  • The H bonding patterns of different helical secondary structures.The -helix Bonding occurs between the carbonyl oxygen of eachresidue and the amide proton of the residue 4 residue ahead in the helix.The 3 helix = the carbonyl oxygen of each residue and the amide proton 10 of the residue 3 residue ahead, forming a more narrow and elongated helix.Pi helix= ith and i+5 forming a wider helix.The 2 ribbon is not a regular secondary structure. 7. 20
  • The -sheet In a -sheet, carbonyl oxygens and amides form hydrogen bonds. These secondary structures can be either antiparallel (as shown) or parallel and need not be planar (as shown) but can be twisted. The propensity of a peptide for forming -sheet also depends on its sequence. 21
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  • Tertiary structure = global folding of a protein chain 23
  • Tertiary structures are quite varied 24
  • Quaternary structure = Higher-order assembly of proteins 25
  • Example of tertiary and quaternary structure - PriB homodimerExample is PriB replication protein solved at UW: Lopper, Holton, and Keck(2004) Structure 12, 1967-75. 26
  • Examples of other quaternary structures Tetramer Hexamer Filament SSB DNA helicase RecombinaseAllows coordinated Allows coordinated DNA binding Allows complete DNA binding and ATP hydrolysis coverage of an 27 extended molecule
  • Classes of proteinsFunctional definition:Enzymes: Accelerate biochemical reactionsStructural: Form biological structuresTransport: Carry biochemically important substancesDefense: Protect the body from foreign invadersStructural definition:Globular: Complex folds, irregularly shaped tertiary structuresFibrous: Extended, simple folds -- generally structural proteinsCellular localization definition:Membrane: In direct physical contact with a membrane; generally water insoluble.Soluble: Water soluble; can be anywhere in the cell. 28
  • Levels of OrganizationPrimary structureAmino acid sequence of the proteinSecondary structureH bonds in the peptide chain backbone -helix and -sheetsTertiary structureNon-covalent interactions between the R groups withinthe proteinQuanternary structureInteraction between 2 polypeptide chains 29
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  • DomainsA domain is a basic structural unit of a proteinstructure distinct from those that make upthe conformationsPart of protein that can fold into a stablestructure independentlyDifferent domains can impart differentfunctions to proteinsProteins can have one to many domainsdepending on protein size 31
  • Proteins other facts...Non-covalent bonds can form interactionsbetween individual polypeptide chainsBinding site where proteins interact with one anotherSubunit each polypeptide chain of large proteinDimer protein made of 2 subunits Can be same subunit or different subunits 32
  • Single subunit proteins 33
  • Different Subunit Proteins Hemoglobin 2 globin subunits 2 globin subunits 34

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