The Beauty of Protein

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The Beauty of Protein

• Dept. of Microbiology
• Ling-Chun Lin

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Protein and Life

• Abundant in all organisms
• Fundamental to life
• Diverse functions
• Enzyme
• Storage
• Transport
• Messengers
• Antibodies
• Regulation
• Structural proteins

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Protein structure

• Are linear heteropolymers of fixed length
  (polypeptide chain)
• Have 20 types of amino acids
• Fold into specific 3-D conformations
• Determined by the sequence of amino acids

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Methods to Determine Protein Strucutre

• X-ray diffraction
• NMR

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Protein Synthesis

• Central Dogma

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ATGTGTCATGGCGACTGTCCAGCTTTGTGCCAGGAGCCTCGCAGGGGTTG
ATGGGATTGGGGTTTTCCCC TCCCATGTGCTCAAGACTGGCGCTAAAAG
TTTTGAGCTTCTCAAAAGTCTAGAGCCACCGTCCAGGGAGC
DNA
Transcription, translation
MDPVPDLPESQGSFQELWETVSYPPLETLSLPTVNEPTGSWVATGDMFLL
DQDLSGTFDDKIFDIPIEPV PTNEVNPPPTTVPVTTDYPGSYELELRFQ
KSGTAKSVTSTYSETLNKLYCQLAKTSPIEVRVSKEPPKGA
Protein sequence
Protein folding
Protein structure
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Amino Acids
Single and 3-Letter Codes for Amino Acids
Grouped according to the characteristics of the
side chains

• Aliphatic
• alanine, glycine, isoleucine, leucine, proline,
  valine
• Aromatic
• phenylalanine, tryptophan, tyrosine
• Acidic
• aspartic acid, glutamic acid
• Basic
• arginine, histidine, lysine
• Hydroxylic
• serine, threonine
• Sulphur-containing
• cysteine, methionine
• Amidic (containing amide group)
• asparagine, glutamine

Side chain
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Primary structure

• Linear polymer of amino acid residues
• Contains all the necessary information required
  for the 3-D structure

Peptide bond formation
MDPVPDLPESQGSFQELWETVSYPP LETLSLPTVNEPTGSWVATGDMFL
L DQDLSGTFDDKIFDIPIEPVPTNEVN
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Secondary structure

• a?? (helix)
• ß-?(ß- strand)
• ??(motif)

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Peptide Torsion Angles
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ahelix
Direction of translation
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Properties of the alpha-helix

• The structure repeats itself every 5.4 Angstroms
  along the helix axis.
• 3.6 amino acid residues per turn
• Every mainchain CO and N-H group is
  hydrogen-bonded to a peptide bond 4 residues
  away.
• Distortions arise from several factors.

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ß- strand, ß- sheet

• zig-zags in a more extended conformation than the
  alpha-helix
• Amino acid residues in the beta-conformation have
  negative phi angles and the psi angles are
  positive
• Beta strands can associate by main chain hydrogen
  bonding interactions to form a beta sheet
• The R-groups (side chains) of neighbouring
  residues in a beta-strand point in opposite
  directions.

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Beta-sheet

• Parallel beta-sheet
• Antiparallel beta-sheet
• Mixed beta-sheet

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Motif

• DNA recognition motif
• Zine finger
• Helix-turn-helix
• protein recognition motif
• Leucine zipper

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Zine finger
His
Cys
His
Cys
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Tertiary and Quaternary Structure

• Tertiary
• Formed by packing secondary elements into one or
  several compact globular units
• Quaternary
• Final protein may contain several polypeptide
  chains arranged in a quaternary structure
• By formation of such tertiary and quaternary
  structure amino acids far apart in the sequence
  are brought cloase together in three dimensions
  to form a functional region, an acitve site

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Protein prediction

• Why?
• Genome projects have now provided us with a
  description of the complete sequences of all the
  genes in more than a dozen organisms
• These databases provide great opportunities for
  the analysis and exploitation of genes and their
  corresponding proteins
• Knowledate of a proteins tertiary structure is a
  prerequisite for the proper understanding and
  engineering of its function
• The experimental determination of tertiary
  structure is still slow compared with the rate of
  accumulation of amino acid sequence data

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Protein prediction

• Basic ideas
• Homologous proteins have similar structure and
  function
• They have identical amino acid residures in a
  significnt number of sequential positions along
  the polypeptide chain (based on statistical
  methods)
• If significant amino acid sequence identity is
  found with a protein of known crystal structure,
  a three-dimensional model of the novel protein
  can be constructed, using computer modeling, on
  the basis of the sequence alignment and the known
  3-D structure.

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Divergent evolution

• Different proteins in different orgnisms have
  diverged from a common ancestor protein
• Each copy of this ancestor in various organisms
  has been subject to mutations, deletions, and
  insertions of amino acids in its sequence
• In general, its 3-D fold and function have
  remained similar

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Protein prediction

• Methods
• Homology modeling
• Based on the Darwinian and empirical principle of
  significant sequence similarity implies
  similarity in 3-D structure
• Fold recognition (threading)
• Is aimed at identifying a correct template
  structure for those prediction targets that show
  no significant sequence similarity to any of the
  proteins of known structure
• Ab initio
• Methods that do not directly rely on known 3-D
  structures

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Secondary structure prediction

• Two broad classes
• Empirical statistical methods use parameters
  obtained from analyses of known sequences and
  tertiary structures
• Based on the assumption that the local sequence
  in a short region of the polypeptide chain
  determines local structure (not a universally
  valid assumption)
• Based on stereochemical criteria, such as
  compactness of form with a tightly packed
  hydrophobic core and a polar surface

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Protein resources

• Protein Structure Prediction
• PDB
• ExPASy Molecular Biology Server