MAINCHAIN PART OF AMINO ACIDS

How is this wide range of diverse protein function created?
Use (1,2,3) chemical diversity, and (4) protein folding
(1) Chemical diversity is created by the existence of 20 different aa’s.
Illustration. If a 20-residue peptide is to be created from all possible
permutations of one each of the 20 different amino acids, a total of 20!
(or 2 x 10 18 ) different sequences are possible.
(2) Further chemical diversity is created by the different sizes of
proteins (50 residues upwards).
20x19x18x17x16x15x14x13x12x11x10x9x8x7x6x5x4x3x2x1 = 2 x 10 18
(3) Chemical modifications lead to more chemical diversity.
- use of modified amino acids (hydroxyproline in collagen, desmosine
in elastin.
- use of metals and prosthetic groups (Fe & haem of haemoglobin).
- glycosylation of Asn residues (antibodies), or of Ser and Thr residues.
- addition of phosphate groups to Ser residues.
(4) Proteins can fold up into many different 3-D arrangements, one for
each protein, each of which is unique for the particular function.
Four levels of protein structure
Primary structure (chemical): denotes the order of the
covalent polypeptide sequence, and other details (location
of disulphide bridges, prosthetic groups, glycosylation, etc).
Secondary structure (folding): three-dimensional (3-D)
arrangement of ONLY the polypeptide mainchain. This
includes α-helix, β-sheet, loops and triple helix structures.
Stabilised ONLY by hydrogen bonds.
Tertiary structure (folding): 3-D arrangement of the a.a.
sidechains with each other and the mainchain. Stabilised by
hydrogen bonding, salt bridges between opposite charges,
hydrophobic interactions, and disulphide bridges.
Quaternary structure (folding): the 3-D assembly of
individual protein subunits to form a multimeric protein (eg:
the two α and two β chains of haemoglobin)
SECONDARY
STRUCTURE -
Defines the
protein
backbone
NH 3
+
The peptide bond is rigid
H
αC
R 1
Rigid - no rotation
O
C
N
H
H
αC
C
O
R 1
O -
Two rotatable bonds
There are three bonds
between every R group.
One of these is a partial
double bond and
cannot rotate – it is
rigid.
The other two bonds
can rotate.
Regular repeats of
these bond rotations
lead to α-helix and β-
sheet structures.
Secondary structures - the α- helix
This is a helical arrangement of
the protein mainchain that
repeats itself approximately
every 4 th residue.
Features:
(1) Rod-like with the R groups
(sidechains) outside
(2) All the C=O and N-H
mainchain groups are H-
bonded
(3) All H-bonds are parallel to
the helix axis
(4) N-H makes H-bond to C=O
that is 4 residues forward
(5) 3.6 residues per turn
(6) Always right-handed for
reason of the L-amino acids
Secondary structures - the β-sheet
This is a maximally extended
protein mainchain that forms
hydrogen bonds with other
adjacent extended mainchains.
Features:
(1) Mainchain is extended; the R
groups (sidechains) alternate up
and down
(2) All the C=O & N-H mainchain
groups are H-bonded
(3) All H-bonds are between
separate mainchains and
perpendicular to the direction of
the mainchain
(4) Parallel sheets: the N-termini
are at the same end
(5) Antiparallel sheets: the N-
termini are at opposite ends
(6) Note the location of β-turns
β-turns