The document provides a detailed overview of protein structure and function, highlighting that proteins are essential organic molecules made of amino acids. It explains the levels of organization in proteins, including primary, secondary, tertiary, and quaternary structures, and discusses the various interactions that stabilize these structures. Additionally, it contrasts globular proteins, which are compact and versatile, with fibrous proteins that serve structural roles.

1. Protein Structure and
Function
A guide by:
Thomas Marangwana
tmarangwana@science.uz.ac.zw
+263777612181
University of Zimbabwe
Department of Biochemistry and Biotechnology,
Room 146

2. Proteins
• Proteins are the most abundant organic molecules
of the living system.
• They constitute about 50% of the cellular dry weight.
• They constitute the fundamental basis of structure
and function of life.
• In 1839, Dutch chemist G.J. Mulder was first
to describe about proteins.
• The term protein is derived from a Greek
word proteios, meaning first place.
• The proteins are nitrogenous macromolecules that
are composed of many amino acids.

3. Peptide formation
• Carboxyl group of one amino acid (with side
chain R1)forms acovalent peptide bond with α-
amino group of another amino acid (with side
chain R2) by removal of a water molecule.
• The result is : Dipeptide.
• The dipeptide can then form a second peptide
bond with a third amino acid (with side chain R3)
to give tripeptide.
• Repetition of this process generates a
polypeptide or protein of specific aminoacid
sequence.

4. Peptide formation

5. Structure of proteins
• Proteins have different levels of
organisation
i. Primary Structure
ii. Secondary Structure
iii. Tertiary Structure
iv. Quaternary Structure

6. Structure of proteins

7. Forces that determine the structure
• Primary structure: determined by
covalent bonds
• Secondary structure: determined by
weak forces

8. Protein structures

9. 1. Primary Structure
• The primary structure of protein refers to
the sequence of amino acids present in
the polypeptide chain, it contains all the
information necessary to make a protein.
• Amino acids are covalently linked by
peptide bonds or covalent bonds.
• Eachcomponent amino acid in a polypeptide
is called a "residue” or “moiety”.

10. 1. Primary Structure
• By convention the primary structure of
protein starts from the amino terminal
(N) end and ends in the carboxyl terminal
(C) end.

11. 2. Secondary structure
• It is a local, regularly occurring structure in
proteins and is mainly formed through hydrogen
bonds between backbone atoms.
• Pauling & Corey studied the secondary
structures and proposed 2 conformations i.e.,
i. α helix
ii. β sheets

12. 2. Secondary structure

13. α-Helices
• The a-helix is a rod like structure. It is
one peptide chain which is coiled so
that adjacent residues are 1.5A apart.
• There are H-bonds between the N-H and
the C=O groups of the backbone. These
link the peptide bonds between every
fourth amino acids.
• The side chains all extend outwards from
the helix.

14. α-Helices
• Although the helix itself is quite a rigid
structure, it can be curved or kinked,
which lends some flexibility to the protein
structure.
• Two or more polypeptides can entwine to
form very long, very stable, structures
called α-helical coiled coils.
• These are often found in keratin (hair),
myosin (muscle), epidermin (skin), and
fibrin (blood clots).

15. α-Helices
• Right handed spiral structure.
• Side chain extend outwards.
• Stabilized by H bonding that are arranged
such that the peptide Carbonyl oxygen (nth
residue) bonds with amide hydrogen (n+4 th
residue).

16. α-Helices
• Amino acids per turn – 3.6
• Pitch is 5.4 A°
• Alpha helical segments, are found in many
globular proteins like myoglobin
• Length ~12 residues and ~3 helical turns.
phi = -60 degrees, psi = -45 degrees

17. α-Helices

18. β-Sheets
• A polypeptide in a β-sheet is called a β-
strand, and is almost fully extended (not
coiled) so there is 3.5A between adjacent
residues.
• Formed when 2 or more polypeptides line up
side by side.
• The β-strands in a sheet can either run in
the same (parallel) or different (anti-
parallel) direction.
• They are stabilized by hydrogen bond
between NH and carbonyl groups of
adjacent chains.

19. β-Sheets

20. β-Sheets
• β sheets come in two varieties.
i. Antiparallel β sheet – neighboring
hydrogen bonded polypeptide chains
run in opposite direction.
ii. Parallel β sheet - hydrogen bonded
chains extend in the same direction.

21. β-Sheets

22. Protein folding
• The peptide bond allows for rotation around
it and therefore the protein can fold and
orient the R groups in favorable positions.
• Weak non-covalent interactions will hold
the protein in its functional shape – these
are weak and will take many to hold the
shape.
• Protein folding occurs in the cytosol.

23. Protein folding

24. Protein folding patterns
• 2 regular folding patterns have been
identified
– formed between the bonds of the
peptide backbone.
i. α-helix – protein turns like a spiral –
fibrous proteins (hair, nails, horns).
ii. β-sheet – protein folds back on itself as
in a ribbon – globular protein.

25. Protein folding patterns

26. 3. Tertiary structure
• The tertiary structure defines the specific overall 3-D
shape of the protein, how the peptide chain folds so
that sidechains are packed and organized.
• Tertiary structure is stabilized by various types of
interactions between the side-chains of the peptide
chain.
• These interactions are:
i. Disulfide bonds
ii. Hydrophobic interactions
iii. Hydrogen bonds
iv. Ionic interactions
v. Vander Waals force

27. 3. Tertiary structure

28. 1. Disulphide Bonds
• If two cysteine side chains are close to one
another and the local environment is
conducive to oxidation, then they can form
a disulphide bond/bridge.
• The residues can either be in the same
peptide chain (forming a loop) or in
different chains.
• They mainly occur in secreted proteins and in
the parts of membrane proteins which face
the outside.
• NB, disuphide bridges only form after the
protein has folded into its tertiary structure.

29. 1. Disulphide Bonds

30. 2. Hydrophobic Interactions
• Close attraction of non-polar R groups
through dispersion forces.
• They are non attractive interactions,
but results from the inability of water
to form hydrogen bonds with certain
side chains.
• Very weak but collective interactions
over large area stabilize structure.
• Repel polar and charged
molecules/particles.

31. 2. Hydrophobic Interactions

32. 3. Hydrogen Bonds
• When unfolded, all polar/hydrophillic
sidechains can interact via H-bonds with
water. When the protein folds, they must H-
bond to each other and exclude much of the
water. All groups capable of forming a
hydrogen bond MUST, hence H-bonding in
the backbone (C=O to N-H) by way of
helices and sheets is an efficient way of
ensuring stability

33. 3. Hydrogen Bonds
• The capacity of proteins to form hydrogen
bonds is an important determinant of
protein stability.
• Hydrogen bonds can be between backbone
groups, as in helices and sheets; between
side chains, such as serine or threonine O-H
groups and carbonyl carbons of side chains
(-C=O); and between backbone groups and
side chain groups.

34. 3. Hydrogen Bonds

35. 4. Ion Pairs
• When amino acid side chains of opposite
charge are in close proximity, they can
form an ion pair (also called a salt bridge).
• Since charge is affected by pH, so is the
formation and the breakage of these ion
pairs.
• Ions on R groups form salt bridges
through ionic bonds.
• NH3 +and COO- areas of the protein
attract and form ionic bonds.

36. 4. Ion Pairs

37. Non-Covalent Bonds
• Hydrophobic interactions, hydrogen bonds
and salt bridges are all non-covalent
interactions.
• These are all relatively weak interactions but
the large number in a protein combine to
give the overall stability of the structure.
• If these interactions are maintained the
protein keeps its tertiary ("native")
structure.
• However once the bonds maintaining the
structure begin to be disrupted the tertiary
structure is destroyed and the protein is
said to be "denatured

38. Interactions

39. Globular proteins
• Globular proteins fold up into compact,
spherical shapes.
• Their functions include biosynthesis,
transport and metabolism, eg, myoglobin
is a globular protein that stores oxygen in
the muscles.
• Myoglobin is a single peptide chain that is
mostly α-helix –
• The O2 binding pocket is formed by a heme
group and specific amino acid side-chains
that are brought into position by the tertiary
structure

40. Globular proteins

41. Fibrous proteins
• Fibrous proteins consist of long fibers and are
mainly structural proteins, eg α-keratins are
fibrous proteins that make hair, fur, nails and
skin.
-hair is made of twined fibrils, which are
braids of three α –helices (similar to the
triple helix structure of collagen)
- the α -helices are held together by
disulfide bonds.
• β -keratins are fibrous proteins found in
feathers and scales that are made up mostly of
β -pleated sheets

42. Fibrous proteins

43. Subunits and Quaternary
Structure
• Proteins containing more than one
polypeptide chain exhibit an additional
level of structural organisation.
• In this case, each polypeptide chain is a
"subunit". Quaternary (4D) structure
describes the way the subunits are arranged
together and the nature of their contacts.
• Subunits associate by non-covalent
interactions similar to those involved in
tertiary structure.
.

44. Subunits and Quaternary
Structure
• There are two kinds of quaternary
structures: both are multisubunit proteins.
i. Homodimer : association between identical
polypeptide chains.
ii. Heterodimer : interactions between
subunits of very different structures.

45. Subunits and Quaternary
Structure

46. Subunits and Quaternary
Structure
• Quaternary structure adds stability by
decreasing the surface/volume ratio of
smaller subunit
• Simplifies the construction of large
complexes
– viral capsids and proteosomes

48. THANK YOU