Fundamentals of

Protein Structure
Dr. Saba Abdi
Assistant professor
Depatrment Of Biochemistry
King Saud University

Proteins play key roles in a living

system
examples of protein functions

Transport:
Some proteins transports various
substances, such as oxygen, ions, and
so on.

Information transfer:
For example, hormones.

Catalysis:
Almost all chemical reactions in a
living cell are catalyzed by protein
enzymes.

Physical cell support and shape (tubulin,

actin, collagen)

Mechanical movement (flagella, mitosis,

muscles)

Alcohol
dehydrogenas
e oxidizes
alcohols to
aldehydes or
ketones

Haemoglobin
carries
oxygen

Insulin
controls the
amount of
sugar in the
blood

Protein classification
Classification based of structure:
1.Globular Proteins:
Usually water soluble, compact, roughly

spherical
Hydrophobic interior, hydrophilic surface
Globular proteins include enzymes,carrier

and regulatory proteins

Protein classification
Classification based of structure:
2. Fibrous Protein:
Provide mechanical support
Often assembled into large cables or threads
-Keratins: major components of hair and nails
Collagen: major component of tendons, skin,

bones and teeth

Protein classification
Classification based of composition:
1.Simple proteins: albumin, lysozyme
1.Conjugated proteins: haemoglobin,

myoglobin, cytochromes,
immunoglobins.

Properties of proteins
Molecular weights range from 10000-several hundred
thousand
Generally proteins are soluble in water, except the
membrane proteins which are hydrophobic
Absorb light in the UV range. Maximum absorption at 280nm
due to aromatic a.a
Have a specific Isoelectric pH [pI]. Positively charged below
PI, and negatively charged above pI
Proteins are charged molecules, but the charge depend on
the pH of the buffer.
Move under an electric field and can be separated by
electrophoresis
Give color reactions; e.g blue color with Ninhydrin reagent.

Amino acid: Basic unit of

protein

R
NH3

Amino group

Different side
- chains, R,
COO determin the
Carboxylic
acid group properties of 20
amino acids.

An amino
acid

20 Amino acids
Glycine
(G)

Proline (P)

Glutamine (Q)

Alanine (A)

Valine
(V)

Isoleucine (I)

Methionine (M) Phenylalanine (F) Tryptophan (W)

Serine
(S)

Asparatic acid (D)Glutamic acid (E)

Leucine (L)

Asparagine
(N)

Threonine (T)

Tyrosine (Y)

Cysteine (C)

Lysine (K)

Arginine (R)

Histidine (H)

White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic

zwitterions
Under normal cellular conditions amino

acids are zwitterions (dipolar ions):

Amino group =
Carboxyl group =

-NH3+
-COO-

Proteins are linear polymers

of amino acids
NH3

R1

R2

C COO NH3

C COO

H
A carboxylic acid

H2 O

condenses with an
amino group with the
release of a water

H2 O

R1

R2

R3

C CO NH C CO NH C CO

NH3

H
A

Peptide
bond

N S

H
T

Peptide
bond
D

H
A

The amino acid

sequence is called
as primary structure

Peptide bond
Peptide bond - linkage between amino

acids is a secondary amide bond

Formed by condensation of the -carboxyl

of one amino acid with the -amino of

another amino acid (loss of H2O molecule)

Primary structure - linear sequence of

amino acids in a polypeptide or protein

Planar peptide groups in a

polypeptide chain
Rotation around C-N bond is restricted
due to the double-bond nature of the
resonance hybrid form
Peptide groups (blue planes) are

therefore planar

Trans and cis conformations

of a peptide group
Nearly all peptide groups in proteins are
in the trans conformation

Amino acid sequence is

encoded by DNA base
sequence in a gene
DNA
molecule

G
C
G
C
T
T
A
A
G
C
G
C

DNA base
C sequence
G
C
G
A
A
T
T
C
G
C
G

Each Protein has a unique

structure
Amino acid
sequence
NLKTEWPELVGKSV
EEAKKVILQDKPEAQ
IIVLPVGTIVTMEYRI
DRVRLFVDKLDNIAE
VPRVG

Folding!

Hierarchical nature of
protein structure
Primary structure (Amino acid sequence)

Secondary structure -helix, -sheet

Tertiary structure Three-dimensional structure

formed by assembly of secondary structures

Quaternary structure Structure formed by

more than one polypeptide chains

Basic structural units of

proteins: Secondary structure
-helix

-sheet

Secondary structures, helix and -sheet, have

regular hydrogenbonding patterns.

-helix
-helix:(is composed of one
polypeptide chain)
It is spiral structure;
consisting of a tightly packed, coiled
polypeptide backbone core with the
side chains of the component amino
acids extending outward from the
central axis in order to avoid
interfering sterically with each other.

-helix
Right handed -helix is stabilized by intra-chain
hydrogen bond.
Counting from the N-terminal end, the C=O group
of each amino acid residue is hydrogen bonded to
the N-H group of the amino acid four residues
away from it in the covalently bonded sequence.
(each C ) of one a.a. is hydrogen bonded to the (NH) of the next fourth amino acid in the chain (1
4).
There are 3.6 residuesfor each turn of the helix.
The pitch (complete turn distance) is 0.54 nm (5.4
A0).

The -helix

Examples of -helix
Some proteins are entirely -helix eg
-keratin fibrous protein in hair.
Other proteins have different
amount of -helix e.g. hemoglobin
has 80% -helix
Some proteins have no -helices eg
keratin in silk

-pleated sheet
The surface of -sheet appear pleated and these structures are
called -pleated sheet
-sheet are composed of two or more separate peptide chains.
(-strands) or segments of polypeptide chains that are almost
fully extended.
The peptide backbone is almost completely extended.
It is stabilized by:
Interchain hydrogen bonds(between the polypeptide
backbone of separate polypeptide chains)(It is formed between
(-NH) group of one chain or one segment and (C=O) of the
adjacent chain (or segment)
Intrachain hydrogen bonds(between the polypeptide
backbone of single polypeptide chain folding back on itself)
There are two types of -pleated sheet:Parallel -sheet
Antiparallel -sheet

-pleated sheet

Three-dimensional
structure of proteins

Tertiary
structure

Quaternary

TertairyStructure
It is spatial arrangement of amino acids that are far
apart in the linear sequence.
The polypeptide chain is folded in three of dimension.
Bonds responsible for its stability:
(1)Hydrogen bonds (between side chains)
(2)Hydrophobic bonds (between the non-polar side
chain of a.a.)
(3)Electrostatic bonds (salt bonds)(Formed between
oppositely charged group in the side chains of amino
acids)e.g. epsilon-amino group of lysine and carboxyl
group of aspartate, interact electrostatically to stabilize
the protein structure.

Quarternary Structure
This structure for proteins that have more than one polypeptide
chains.
Refers to the organization of subunits in a protein with multiple

subunits (an oligomer)

Subunits (may be identical or different) have a defined

stoichiometry and arrangement

Subunits are held together by many weak, noncovalent interactions

(hydrophobic, electrostatic)
The interaction between subunits are stabilized by:
hydrogen bonds
electrostatic bonds
hydrophobic bonds
e.g. of proteins having quaternary structure:Insulin (2 subunits),
Lactate dehydrogenase enzyme: (4 subunits), hemoglobin (4
subunits)

Close relationship between

protein structure and its
function
Hormone receptor

Example of enzyme
reaction
substrate
s

enzym
e

enzym
BCH
221 Enzymology
e

Final Examination

B
Matching
the shape
to A

enzym
e

Digestion
of A!

Binding to A

Antibody