Protein Structure

Protein structure
Structure
 Side chains (R) of amino acids are either polar or
hydrophobic.
Amino acids as building blocks of proteins

Hydrophobic amino acids
“go a vast lake, ice pour
mushroom top playing cream”
Polar charged amino acids
ib.bioninja.co
m.au
“So try to ask God”
Function
 Structural proteins: actin, microtube
 Transcription factors
 Catalysts
 Signal within or between cells, membranes transporters
 Storage and transport
o Haemoglobin: 4 subunits, 4 haem groups, 4 iron atoms
o Ferritin: 24 subunits, up to 4,000 iron atoms
 Signalling molecules and receptors, e.g. insulin
o Communication between and within cells
o Binding and regulation of other proteins
 Fight infection (antibodies)
o Immune response to invasion by viruses, bacteria, allergens and other toxins
(antigens)
 Motor proteins
o Transport of molecules and organelles across the cell
o Membrane fusion/fission, exocytosis/endocytosis
o Cell contraction/motility
Deoxyribonucleic acid (DNA)
Transcription (1)
Central dogma
Pre-mRNA
Splicing of introns (2)
mRNA
Nuclear export (3)

Translation (4)
Amino acid string
Folding (5)
Trans vs cis conformation

• Almost all peptide bonds are in trans configuration. Protein
• Only for proline the cis and trans configurations have similar energies.
Levels of protein structure
1. Primary structure
o Amino acid sequence of the protein stabilized by peptide bonds.
o Read from the amino terminus to the carboxyl terminus.
2. Secondary structure
o Local rearrangement of residues in helices, sheets, turns, and loops
stabilized by H-bonds between CO and NH groups of the backbone.
o e.g., coiled or pleated.
i. -helix
 Hydrogen bonds between the carbonyl group (C=O) of residue X
and the N-H group of residue X+4
 Right-handed (i.e. clockwise)
 partial positive charge at the N-terminus and a partial negative
charge at the C-terminus partial positive charge at the N-terminus

and a partial negative charge at the C-terminus
 310-helix: Occurs mostly at the ends of -helices
• the H bond closes a loop of 10 atoms containing 3 residues.
 π-helix
• 4.4 residues per turn H
ii. -sheet
 Peptide chains fully extended → Pleated shape
 Parallel β-sheets:
• two polypeptide strands running in the same direction.
• Non-linear hydrogen bonds → Less stable, parallel β-sheets with
less than five parallel strands are rare.
 Antiparallel β-sheets:
• two polypeptide strands running in the opposite directions.
• Well oriented hydrogen bonds → Strong and stable
iii. -turns
 reverse the direction of the polypeptide backbone
 contain at least one residue of glycine or proline.
iv. Loops
Zinc finger motif
 Various lengths, irregular shape, very flexible.
2.1 Super secondary structure
• Combination of a few secondary structure elements usually performing a particular
function.
3. Tertiary structure Lysozyme

o Overall 3D structure of the protein Alpha+beta fold
stabilized by interactions between
side chains. • Five helices (three α, of which
one closer to a π-helix, two
o Hydrogen bond, Disulphide bond intermediate α/310)
o R side: ionic bond, hydrophobic • Three stranded antiparallel β
interaction sheets
4. Quaternary structure
o Arrangement of subunits in a protein made of more than one chain and
stabilized by interactions between side chains.
o Subunits can be identical or different.
Neurotrophin-4 Haemoglobin
(two identical subunits) (two - + two -subunits)
Protein domains
• Protein domains are spatially distinct fragments of a polypeptide chain. Protein
domains are typically composed of 50 to 350 amino acid residues.
• A single polypeptide chain can form several domains but only ONE subunit.
• According to the domain shuffling theory, many multidomain proteins have arisen
during evolution by the fusion of genes that encoded separate proteins in an
ancestor.
Structure of enzymes Protein-only enzyme
• Apoenzyme: an enzymatically inactive

+
protein part of an enzyme, which requires a
cofactor for its activity.
Apoenzyme Cofactor Holoenzyme
• Cofactors:
o Prosthetic groups (covalently bound to the protein, e.g., haem in
haemoglobin)
o Metal ions (Zn2+, Fe3+, etc.)
o Coenzymes (often vitamins)
• The active site of an enzyme is a cleft or a groove where the substrate binds and the
catalytic reaction occurs.
1. lock and key model

o the substrate fits the rigid active site like a key fits a lock.
o The model cannot explain why some enzymes act on a large range of
substrates.
2. induced fit model
o the substrate induces a change in the enzyme structure.
o This model explains why some enzymes can act on a very large range of
substrates.
o E.g. Conformational changes in hexokinase are associated with glucose
binding to the active site
o Some enzymes are composed of domains with different functions:
 Phosphofructokinase 2 (PFK2) is a bifunctional enzyme:
- kinase domain
- phosphatase domain
3. The three-point attachment model
o the substrate forms at least three connections with the enzyme.
o 2 chemically identical groups in the substrate, a1 and a2, can be distinguished
by an enzyme as substrate binds the active site at three or more points.
Defects in protein structure and diseases
1. Sickle cells
• Normal RBC live: 120 days in the bloodstream, sickled cells: 10-20 days
• Sickled cells cause blockages that deprive organs and tissues of oxygen.
• Not enough red blood cells in the bloodstream to carry oxygen resulting in anaemia.
o severe pain, organ damage (oxygen deprivation), serious infections, or even
stroke
• Reason: Glutamate to valine mutation in haemoglobin causes its aggregation into
fibres → red blood cells assume sickle shape in sickle cell anaemia.
2. Goucher disease
• lipid storage disease
• Caused by mutations in acid--glucosidase that breaks down glucosylceramide.
• Mutations in acid--glucosidase stabilize a conformation that limits access to the
active site → the catalytic activity of the enzyme is decreased causing Gaucher
disease.

Protein Structure

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Protein Structure

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Protein structure

Amino acids as building blocks of proteins

Polar charged amino acids

Splicing of introns (2)

Nuclear export (3)

Amino acid string

Trans vs cis conformation

charge at the C-terminus partial positive charge at the N-terminus

3. Tertiary structure Lysozyme

Structure of enzymes Protein-only enzyme

• Apoenzyme: an enzymatically inactive

1. lock and key model

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