Peptides and Proteins

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Peptides and Proteins
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Peptide primary structure problem

• An unknown octapeptide gives the following upon
  total hydrolysis
• A(2), C, D, G, L, M, S
• Reaction of the octapeptide with Sangers reagent
  followed by total hydrolysis gives labeled
  leucine (L).
• Carboxypeptidase treatment of the octapeptide
  gives initially a high concentration of alanine
  (A), followed by glycine (G) and then serine (S).
  
• Leucineaminopeptidase treatment of the
  octapeptide gives initially a high concentration
  of leucine (L), followed by aspartic acid (D)
  then cysteine (C).
• Partial hydrolysis of the octapeptide gives the
  following identifiable fragments
• D C M, A S, C M A, S G A, and L
  D
• Write the correct primary structure (using
  one-letter abbreviations and following the usual
  convention of listing the N-terminal amino acid
  on the left).

D C M
A S
C M A
S G A
L D
L
A
G
S
D
C
M
A
N-terminal aa
C-terminal aa
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Classification (vague)

• Peptides have fewer than 50 amino acids
• Oligopeptides (di, tri-, tetra-, etc.) up to
  about 10 aa
• Polypeptides (longer chain of aa than an
  oligopeptide)
• Proteins have more than 50 amino acids, and may
  be combined with other structure classes, such as
  carbohydrates, lipids, etc.
• Simpleyield only amino acids upon hydrolysis
• Conjugatedyield amino acids and other structure
  types (carbohydrate, lipid, etc.) on hydrolysis

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Levels of Protein Structure

• Primary structure the amino acid sequence
• Secondary structure the conformation due to
  rotations around C-C and C-N single bonds
• Tertiary structure the folding of the peptide
  chain into its characteristic 3D-shape
• Quaternary structure the aggregation of several
  subunits held together by other than covalent
  bonds (not all peptides have this feature)

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Primary Structure

• the amino acid sequence, written from the
  N-terminal (on the left) to the C-terminal (on
  the right). Formerly abbreviated using
  three-letter abbreviations Ala, Gly, Phe, Val,
  etc. now we use one-letter abbreviations A, G,
  F, V.
• Ala Gly Phe Val
• or
• A-G-F-V

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Secondary Structure

• the 3-D arrangement (conformation) of segments of
  a peptide/protein chain due to rotation around
  C-C and C-N bonds

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Secondary Structure

• There are several named conformations due to
  common typical
  combinations of rotation angles around C-N (f)
  and C-C (y) bonds
• f y
• a-helix -58º -47º
• b-pleated sheet ( -140º 135º
• hairpin turns are sharp curves in the peptide
  chain, often due to proline residues

)
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Problem w/ flat sheet
(F and y 180º)
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b-pleated sheet
(F -140º y 135º)
7.0 Å
b-pleated sheet can be stabilized by H-bonding
between adjacent peptide chains
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a-helix
(F -58º y -47º)
a-helix is stabilized by H-bonding within a
peptide chain
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Tertiary and Quaternary Structure

• Tertiary structure the coiling or folding
  pattern of single polypeptide chains
• Many individual shapes, but generally fall into
  one of two categories
• Fibrous (insoluble generally function as
  structural component)
• Globular (soluble coiled into compact, spherical
  shapes, with hydrophobic groups oriented inward
  and hydrophilic groups oriented outward toward
  the aqueous environment of the cell)
• Quaternary structure non-covalent aggregation of
  two or more protein molecules and possibly other
  structures into functional units.

(examples will be shown in WebLab Viewer Lite)
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Functions of Proteins

• Hemoglobin the oxygen-carrying molecule in the
  blood
• Insulin regulates glucose metabolism
• HIV protease cleaves peptide bonds of large
  protein to allow activation of HIV virus within
  host cell
• Carboxypeptidase digestive enzyme that
  hydrolyzes peptides into their component amino
  acids
• Keratin provides structure of wool, hair,
  fingernails, and feathers