Protein Structure

1
Protein Structure
From Protein Data Bank PDB ID 1B0E Kalus, W.,
Zweckstetter, M., Renner, C., Sanchez, Y.,
Georgescu, J., Grol, M., Demuth, D., Schumacher,
R., Dony, C., Lang, K., Holak, T. A. structure
of the IGF-binding domain of the insulin-like
growth factor-binding protein-5 (IGFBP-5)
implications for IGF and IGF-I receptor
interactions. EMBO J 17 pp. 6558 (1998)
2
Functions

• Diverse functions related to structure
• Structural components of cells
• Motor proteins
• Enzymes
• Antibodies
• Hormones
• Hemoglobin/myoglobin
• Transport proteins in blood

3
Structure

• Amino acids
• Amino group (NH2)
• Carboxyl group (COOH)

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p23
4
Amino acids

• 20 amino acids make up protein
• 8 essential amino acids
• 9 in infant (histidine)
• Dipolar
• ve end (NH3)
• -ve end (COO-)

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p23
5
Protein structure - bonding

• 5 bonds or forces determine structure
• Peptide bond
• Hydrogen bond
• Disulfide bond
• Ionic bond
• Hydrophobic force

6
Peptide bond

• Peptide bond joins amino acids
• Bond at both ends
• Increases range of possible proteins
• 2 peptides can result from bonding of 2 amino
  acids
• 1.0 x 1026 peptides can be formed from 20 amino
  acids

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p23
7
Primary protein structure
Primary structure of insulin

• Linear sequence of amino acids forms primary
  structure
• Sequence essential for proper physiological
  function

Bettelheim March (1990) Introduction to Organic
Biochemistry (International Edition)
Philadelphia Saunders College Publishing, p299
8
Sickle cell anemia

• Replacement of single glutamine with valine in
  one polypeptide chain of hemoglobin alters
  structure and function

Bettelheim March (1990) Introduction to Organic
Biochemistry (International Edition)
Philadelphia Saunders College Publishing, p301
9
Secondary protein structure

• Peptide chains fold into secondary structures
• ? - helix
• ? - pleated sheet
• Random coil

10
? - helix

• Shape maintained by hydrogen bonds between CO
  and N-H groups in backbone
• R groups directed outward from coil

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p28
11
? - pleated sheet

• Structure maintained by hydrogen bonds between
  CO and N-H groups in backbone
• R groups directed above and below backbone

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p29
12
Random coil

• Not really random structure, just non-repeating
• Random coil has fixed structure within a given
  protein
• Commonly called connecting loop region
• Structure determined by bonding of side chains
  (i.e. not necessarily hydrogen bonds)

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p27
13
Tertiary protein structure

• Secondary structures fold and pack together to
  form tertiary structure
• Usually globular shape
• Tertiary structure stabilised by bonds between R
  groups (i.e. sidechains)

14
Tertiary structure - H bond

• H bonds weak allowing to be broken and reformed
  easily
• Allows structural change
• produces functional molecules

15
Tertiary structure - disulfide bond

• Covalent bond between sulfur atoms on two
  cysteine amino acids

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p32
16
Tertiary structure - ionic bond

• Ions on R groups form salt bridges through ionic
  bonds

From Summerlin, LR. (1981) Chemistry for the
Life Sciences. New York Random House, p459
17
Tertiary structure - hydrophobic forces

• Close attraction of non-polar R groups through
  dispersion forces
• Very weak but collective interactions over large
  area stabilise structure
• Repel polar and charged molecules/particles

Bettelheim March (1990) Introduction to Organic
Biochemistry (International Edition)
Philadelphia Saunders College Publishing, p302
18
Quaternary protein structure

• Arrangement of multiple tertiary structures into
  single functional complex
• Allows for changes in structure/function in
  response to chemical stimuli

From Elliott, WH. Elliott, DC. (1997)
Biochemistry and Molecular Biology. Oxford
Oxford University Press. p27