Proteins

Protein
Definition
Proteogenesis
Primary structure
Secondary structure
Tertiary structure
Quaternary structure
Proteolysis
Chaperone.

2. •Proteins are
unbranched polymers
of
L-alpha amino acids

4. •Synthesis of proteins in the cells
known as proteogenesis
•Daily production: 400 g

5. DNA mRNA
transcription
synthesis of
polypeptides
translation
folding of proteins
post-translational
modification
Native conformation
(biological active proteins)
sorting
transport to their
site of action

6. Transcription (nucleus)
•Transcription–synthesis of mRNA on DNA
•Signaling molecules-SM (e.g. hormones) binds with
the nuclear receptor and form NR:SM complex.
•This complex binds with specific region of DNA and
promotes synthesis of mRNA on DNA.

7. Translation
•Translation–assembly of
proteinogenic amino
acids in correct order into
peptide/polypeptide
according to genetic
instruction in mRNA.

8. Sites of translationfree ribosimes
80% 20%
begins in free ribosomes
free ribosome is attached
to RER and synthesis
continues in the lumen of
RER
proteins are secreted
in Golgi apparatus
proteins
inserted into
the cell membrane
(cytoplasm)
Mitochondrial
proteins
(encoded by
nuclear gene)
Cytoplasmic
proteins
Lysosomal
enzymes
secreted
proteins

10. Protein primary structure
•Primary structureis
defined as the
sequence of amino
acids held together by
peptide bonds
•OR
•Primary structure –
sequence of amino
acids specified in the
gene.

11. Formation of peptide bondsH
2NCHC
CH
3
OH
O
H
2NCHC
CH
2
OH
O
SH
H
2NCHC
CH
3
O
H
NCHC
CH
2
OH
O
SH
peptide bond
Alanine (Ala)
Cysteine (Cys)
Alanylcysteine (dipeptide)
Ala-Cys
H
2O
+
N-terminal
end
C-terminal end

12. Properties of peptide bond
•1. Is planar
•2. Is not freely rotatable
•3. Undergo proteolytic cleavage by specific
enzymes known as proteases.

13. •Secondary–folding of amino acids
into an energetically stable
structure.
•Two examples:
•Alpha-helix
•Beta-sheet
•These shapes are stabilized by
hydrogen bonds

14. •Alpha-Helix
•Right hand has been
found in protein
structure only.
•Protease sensitive
•More higher % in all
proteins
•Beta-sheet
•Zigzag form
Protease resistant
•Limit % in proteins

15. Positioning of the secondary structure
in relation to each other to generate
three-dimensional shape (due to side
chain interactions)
Also includes the shape of protein as a
whole (globular or fibrous)

16. •Tertiary structure is
stabilized by
•(i) weak bonds
(hydrogen, hydrophobic
interactions)
•(ii) Strong covalent
bonds(disulfide bonds)
•(iii) Ionic bonds

17. •In some cases proteins
are assembled from
more than one
polypeptides or
monomer and results in
the formation of
oligomeric proteins.

18. •Only those proteins that have more than one poly
peptide chain (polymeric) have a quaternary stru
cture. Not all proteins are polymeric.
•Many proteins consist of a single polypeptide ch
ain and are called monomeric proteins, e.g. myo
globin.
•The arrangement of these polymeric polypeptide s
ubunits in three-dimensional complexes is called th
e quaternary structure of the protein.
•Examples of proteins having quaternary structure a
re:
–Lactate dehydrogenase
–Pyruvate dehydrogenase
–Hemoglobin.

19. Quaternary Structure Stabilizing Forces
The subunits of polymeric protein are held together
by noncovalent interactions or forces such as:
• Hydrophobic interactions
• Hydrogen bond
• Ionic bonds.

22. Bonds Responsible for Protein
Structure
•Protein structure is stabilized by two types of bonds
1. Covalent bond, e.g.
• Peptide bonds
• Disulfide bond
2. Noncovalent bond, e.g.
• Hydrogen bond
• Hydrophobic bond or interaction
• Electrostatic or ionic bond or salt bond or salt
bridge
• Van der Waals interactions.

23. •Covalent Bond
Peptide bonds (–CO-NH–)
• A peptide bond is formed by the condensation of th
eamino group of one amino acid with the carboxylgr
oup of another amino acid with a removal of awater
molecule.
Disulfide bond (-S-S-)
• A covalent bond formed between the sulfhydryl
group (-SH) of side chain of cysteine residues in thes
ame or different peptide chains.
• These disulfide bonds help to stabilize against
denaturation and confer additional stability.

24. •Noncovalent Bonds
Hydrogen bond
• Bond formed between -NH and -CO groups of
peptide bond by sharing single hydrogen.
• Hydrogen bond may occur within the same
polypeptide chain (intrachain) or between differentpol
ypeptide chains (interchain).
• Side chains of 11 out of the 20 standard amino acidsc
an also participate in hydrogen bonding.
Hydrophobic bond or interaction
These are formed by interaction betweennonpolar
hydrophobic R groups (side chain) of amino acids likeal
anine, valine, leucine, isoleucine,methionine,
phenylalanine and tryptophan.

25. •Electrostatic or ionic bond or salt bond or salt bridge
These are formed between oppositely charged groups
when they are close, such as amino (NH3+) terminal a
ndcarboxyl (COO–) terminal groups of the peptide an
d theoppositely charged R-groups of polar amino acid
residues.
Van der Waals interactions
Van der Waals forces are extremely weak and act only
on extremely short distances and include both anattr
active and a repulsive forces (between both polar and
nonpolar side chain of amino acid residues).

26. Chaperone-assisted protein folding
and holding

27. What helps protein folding?
•There is a class of
specialized proteins
CHAPERONES,whose
function is to assist in
the folding and holding
of proteins

28. •All the information required for proteins to correctly a
ssume their tertiary structure is defined
by their primary sequence.
•Sometimes molecules known as ‘‘chaperones’’ interac
t with thepolypeptide to help find the correct tertiary
structure.
•Such proteins either catalyze the rate offolding or prot
ect the protein from forming ‘‘nonproductive’’ intramo
lecular tangles during the
folding process.

30. •Decomposition of proteins to 20 amino
acids (proteinogenic aminoacids)
known as proteolysis
•Daily destruction: 400 g

31. Two ways
proteasomes
and ubiquitin
system
Lysosomal
degradation
Chaperone-mediated autophagy

32. Defective copies
of proteins
Old proteins
addition of
multiple copies
of ubiquitin
addition of
multiple copies
of ubiquitin
Polyubiquitinated
proteins
Recognized by
proteosomes
decomposition
to peptides and amino acids

33. •A particle in the
cytoplasm that
contains hydrolytic
enzymes.
•Especially abundant in
liver and kidney cells.

34. accumulation of
misfolding proteins
Decreased activity
of lysosomal enzymes
Neurodegenerative
diseases
Lysosomal storage
diseases
aggregation to fibrils
damage of neurons
and glial cells
accumulation of
undigested substrates
damage of the cells