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)
Functions

 Diverse functions related to structure

 Structural components of cells
 Motor proteins
 Enzymes
 Antibodies
 Hormones
 Hemoglobin/myoglobin
 Transport proteins in blood
Structure

 Amino acids
 Amino group
(NH2)
 Carboxyl group From: Elliott, WH. Elliott, DC. (1997) Biochemistry

(COOH)
and Molecular Biology. Oxford: Oxford University
Press. p23
Amino acids
 20 amino acids make
up protein
 8 essential amino
acids
 9 in infant (histidine)
From: Elliott, WH. Elliott, DC. (1997) Biochemistry

Dipolar
and Molecular Biology. Oxford: Oxford University
Press. p23 
 +ve end (NH3+)
 -ve end (COO-)
Protein structure - bonding

 5 bonds or forces determine structure

 Peptide bond
 Hydrogen bond

 Disulfide bond

 Ionic bond

 Hydrophobic force
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
From: Elliott, WH. Elliott, DC. (1997) Biochemistry
 1.0 x 1026 peptides can and Molecular Biology. Oxford: Oxford University
Press. p23
be formed from 20
amino acids
 Primary structure of insulin

Primary protein structure

 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
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
Secondary protein structure

 Peptide chains fold into secondary

structures:
  - helix
  - pleated sheet

 Random coil
 - helix
 Shape
maintained by
hydrogen bonds
between C=O
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
 - pleated sheet
 Structure
maintained by
hydrogen bonds
between C=O 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
Random coil
 Not really random
structure, just non-
repeating
 ‘Random’ coil has fixed
structure within a given
protein
 Commonly called
‘connecting loop region’
From: Elliott, WH. Elliott, DC. (1997) Biochemistry
 Structure determined by
and Molecular Biology. Oxford: Oxford University
Press. p27 bonding of side chains
(i.e. not necessarily
hydrogen bonds)
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)
Tertiary structure - H bond
 H bonds weak
allowing to be
broken and
Hydrogen bond
reformed easily
 Allows structural
change
 produces
‘functional’
molecules
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
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
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
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