Protein Structure

Protein
Structure
 Protein Functions

• Catalysis: Alcohol
Almost all chemical reactions in a dehydrogenas
living cell are catalyzed by protein e oxidizes
alcohols to
enzymes. aldehydes or
ketones
• Transport:
Some proteins transports various
substances, such as oxygen, ions, and Haemoglobin
so on. carries
oxygen
• Information transfer:
For example, hormones.
Insulin
• Structure controls the
amount of
sugar in the
blood
 Protein Structure

Proteins

• Are complex molecules built of chains of amino acids

• Have electrical charge that causes them to interact with
other atoms and molecules
• Hydrophilic – water loving
• Hydrophobic – water hating
 Amino acid: Basic unit of
protein

Different side chains,

R R, determine the
properties of 20
amino acids.
NH3 +
C COO -
• Some R-groups are
acid (other alkali)
• Some R-groups are
Amino group
H Carboxylic
acid group water soluble (others
are not)
 20 Amino
acids
Glycine Alanine (A) Valine Isoleucine (I) Leucine (L)
(G) (V)

Proline (P) Phenylalanine (F) Tryptophan (W) Asparagine

(N)
Methionine (M)

Glutamine (Q) Serine Threonine (T) Tyrosine (Y) Cysteine (C)

(S)

Asparatic acid (D)Glutamic acid (E) Lysine (K) Arginine (R) Histidine (H)

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

Amino Acids

Polar Non-Polar

• Uncharged. Ser, Thr, • Aliphatic. Ala, Ile, Leu,

Asn, Gln, Cys Met, Pro, Val

• Positive (basic). Arg, • Aromatic. Phe, Trp, Tyr

Lys, His

• Negative (acidic). Asp,

Glu,
 Peptide Bonds

R
O
C C NH2
R H
O HO
C C
H
NH2
R Amino acids
HO O
R C C NH2
O H
C C NH
H
HO

Water
Disulfide Bonds

C SH HS C
H2 H2 • Two cysteine molecules under
oxidizing conditions

[O]

C S S C
H2 H2
a-Helix
classic Pauling–Corey–Branson α-helix

• N-H to C=O hydrogen bonds in 4th

succeeding amino acid
• Hydrogen bonds parallel to axis

An α-helix in ultrahigh-resolution
electron density contours, with
oxygen atoms in red, nitrogen
atoms in blue, and hydrogen bonds
as green dotted lines (PDB file
2NRL, 17-32).
b-Sheet

• C=O and N-H

perpendicular to chain form
inter-segment H-bonds
• Parallel or antiparallel
• b-strands typically 5-15
amino acid
• More stable than a-helix

b-sheet
 Beta-Pleated Sheet

• Formed through by side-by-side alignment of

polypeptide strands
• Strands may be parallel or antiparallel
• Stability arises via H-bond interactions
• Each strand of a beta sheet may be
pictured as a helix with two residues per
turn
•Clinical application: Alzheimer
 The Beta Turn

• Promote the formation of beta-sheets

• Proline and glycine are prevalent in beta turns
• Occur at protein surfaces
• Give protein in globular than linearity
• Permits the change of direction of the peptide chain to
get a folded structure.
Each protein has a unique structure!

Amino acid
sequence
NLKTEWPELVGKSV
EEAKKVILQDKPEAQ
IIVLPVGTIVTMEYRI
DRVRLFVDKLD

Folding!
 Protein Structure

Primary Assembly
STRUCTURE

PROCESS
Secondary Folding

Tertiary Packing

Quaternary Interaction
 Protein Structures

• Structural Arrangement – four levels

– Primary structure is the sequence in which amino acids are
linked together
– Secondary structure occurs when chains of amino acids fold or
twist at specific points
• Alpha helices and beta sheets
– Tertiary structures are formed when secondary structures
combine and are bound together
– Quaternary structures are unique, globular, three-dimensional
complexes built of several polypeptides
 Protein
Assembly
• occurs at the ribosome
• involves polymerization
of amino acids
attached to tRNA
• yields primary structure
 Primary
Structure
primary structure of human insulin
CHAIN 1: GIVEQ CCTSI CSLYQ LENYC N
• linear
CHAIN 2: FVNQH LCGSH LVEAL YLVCG ERGFF YTPKT • ordered
• 1 dimensional
• sequence of amino
acid polymer
• by convention,
written from amino
end to carboxyl end
• a perfectly linear
amino acid polymer
is neither functional
nor energetically
favorable  folding!
 Secondary Structure

• occurs in the cytosol

• involves localized spatial • yields secondary structure
interaction among primary
structure elements, i.e. the
amino acids
Secondary Structure

• Protein Folding
• The structure and function of a protein depends on protein
folding
• If protein is folded incorrectly, desired function of a protein is
lost and a misfolded protein can be detrimental
• Alpha helices and beta sheets
• Structures are fragile; hydrogen bonds are easily broken
Secondary Structure

α-helix β-sheet

Secondary structures, α-
helix and β-sheet, have
regular hydrogen-
bonding patterns.
 Protein
Packing

• occurs in the cytosol

(~60% bulk water,
~40% water of
hydration)
• involves interaction
between secondary
structure elements
and solvent
• yields tertiary
structure
Tertiary Structure

• non-linear
• 3 dimensional
Protein Interaction
• occurs in the cytosol, in close proximity to
other folded and packed proteins
• involves interaction among tertiary
structure elements of separate polymer
chains
Quaternary Structure
• non-linear
• 3 dimensional
 Quaternary Structure

Folded protein unable to Dimerized protein shields the

contain some hydrophobic hydrophobic amino acids
residues from water
Class/Motif

• class = secondary
structure composition,
e.g. all , all , / ,
+
/
• motif = small, specific
combinations of
secondary structure
elements,
e.g. -- loop
• both subset of fold
Fold
• fold = architecture =
the overall shape and
orientation of the
secondary structures,
ignoring connectivity
between the
structures,
e.g. / barrel, TIM
barrel
• Process depends on
solvents, salt
concentration, pH,
temperature, cofactor,
chaperones
Chaperon

• Help the proteins to achieve their spatial

structures and correct the misfolded structures.
• Correction the chaperons permit the relaxation
of the misfolded structure and enable once
again the correct folding of the proteins
• The functioning of chaperons requires a
significant amount of energy in the form of ATP
Chaperons in the formation and maintenance of the protein
3D structure
Protein solubility

• Amino acid composition

• The physical and chemical parameters of
hydrophilic systems
• pH – the protein solubility is the lowest around
their isoelectric point (pI)
• Ionic strength – high ionic strength decreases
protein solubility
• Amino acid composition – proteins containing
more hydrophobic amino acids have lower
solubility in aqueous systems
• The presence of detergents and reducing
agents increases protein solubility.
Classification of detergents
according to their charge
• Detergents can lead to structural changes, the
proteins lose their three dimensional structure
required for their proper functioning and are
denatured
• Detergents prevent the aggregation of isolated
membrane proteins.
The effect of detergents on protein structure
• Hydrogen bonds
• Electrostatic
• Hydrophobic

Formation of the protein structure.

The most abundant bonds in the living system: hydrogen
bonds
The most abundant bonds in the living system:
electrostatic interactions
The most abundant bonds in the living system:
hydrophobic interactions
The polar water molecules stabilize the structures in the
living systems
The prediction of protein structure based on the
position of hydrophobic amino acids
The tertiary structure of the proteins is made up of secondary
structure elements
Not each protein has a stable tertiary structure. The intrinsically
disordered proteins are proteins that do not have a stable spatial
structure.
The intrinsically disordered proteins can adopt alpha helix or
beta sheet structure upon interacting with other proteins.
Some tools for protein structure analysis
 https://web.expasy.org/protscale/

• monomers (Hsp70)
• dimers (Hsp90)
• oligomers (Hsp 20-30, Hsp60, Hsp110)
• mpaislvitsgkggvgkttatanigtalamigkrvcvidldlglrnldimiglgnrilydivdvvqgra
tlhqalvkdtrfedrlvllpaaqnadknvltpasvrqivdalrsefdyilldcpagieqgfrnalaga
dgalivttpelsalsdadrviglieayhmpigprlivnrvqaamiaagtsltvaaiahrlalpllgyv
vddnaiitadnngepvvfdthskagacyhnitdrl ldpqtpllplitkqptfwqklfrra
• makiivvtsgkggvgktttsasiatglalrgyktavidfdvglrnldlimgcerrvvydlinviqgeat
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Summary

• Proteins are key players in our living systems.

• Proteins are polymers consisting of 20 kinds of
amino acids.
• Each protein folds into a unique three-dimensional
structure defined by its amino acid sequence.
• Protein structure has a hierarchical nature.
• Protein structure is closely related to its function.
• Protein structure prediction is a grand challenge of
computational biology.
THE
END