BIOL1414

Structure & Function

Dr. Andrew Knox

Lecturer (DIT Kevin St, School of Biological Sciences). – andrew.knox@dit.ie

Adjunct Assistant Professor (School of Biochemistry & Immunology, Trinity Biomedical

Sciences Institute, Trinity College Dublin). – aknox@tcd.ie

Tel: +353 (1) 402 4777

Structure and Function of Proteins
The four levels of structure

Peptide
H-bonds Subunit-
bond links Side chain
between subunit
AAs interactions
backbone interactions
together
Level 1 – Primary Structure

 The order of the amino acids in a polypeptide

 Recall that the primary structure has direction

 N-terminal  C-terminal end of the protein
i.e. the ends of the protein with -NH3+ and -COO- groups,

+ -
H3N AA1 AA2 COO
Variability in protein sequences

 Although primary sequence is well defined

 There is certain flexibility in the overall sequence
 Some AA can change but function stays.

 Overlapping properties of AA
 replacing a non-polar AA with another non-polar AA is a
fairly minor change, e.g. replacing Ala (R=CH3) with Gly
(R=H)
 ‘keep it in the family’
Which amino acids are conserved?

What does this mean?

Level 2 - Secondary Structure

Local folding of the polypeptide chains into

regular patterns – helix, sheet

Arises due to the hydrogen bonding between different amino acids in the
polypeptide chain backbone
Between the amide hydrogen of one AA AA side chains (R-groups)
and the carbonyl oxygen of another AA not involved
Secondary Structure: α-Helix

 Carbonyl oxygen of residue i

hydrogen bonds with the amide of
residue i+4

 The R-groups extend away from

the axis
 Although the R-groups are not
involved in this, certain AA are more
likely to be found in an a-helix e.g.
glu, met, ala

 Formation of the a-helix leads to

compaction of the polypeptide
 A typical a-helix has 11 AA (i.e. about 3.5
turns)
 Secondary Structure: β-sheet

 AA almost in the fully extended conformation

 Typically contain 5-10 AAs
 R-groups trans; above and below the plane of the sheet

 These ‘sheets’ can line up next to each other

 Hydrogen bonds can form between neighbouring sheets

 Two types:
 Parallel: direction of AA chain the same
 Anti-parallel: direction of AA chain opposite
Antiparallel ( ) and parallel ( )

Antiparallel b-sheets Parallel b-sheets

• Successive b-strands • N-termini of successive

alternate directions strands in the same
• N-terminus of one direction
strand is adjacent to the • The N-terminus of one
C-terminus of the next strand is adjacent to the
• H-bonds linear  strong N-terminus of the next
strand
N-Terminus C-Terminus

AA AA AA AA AA AA AA
1 2 3 4 5 6 7

N-Terminus C-Terminus

AA AA AA AA AA AA AA
1 2 3 4 5 6 7

C-Terminus N-Terminus

N-Terminus C-Terminus
Beta turns – getting around corners

AA3
AA4

AA2
AA1

 Allow a polypeptide chain to make abrupt turns

 Two types are recognised

 In Type I AA3 can be any AA
 In Type II AA3 is glycine (R-group = H, so small)
Level 3 - Tertiary Structure

Overall folding of a single polypeptide chain

Side chains stick the structure together

Hydrogen Van der Walls Hydrophobic Disulphide
Salt bridges
bonds interactions interactions bonds

All work in concert and contribute to the overall structure of

the protein
Major Interactions in Tertiary Structure
Level 4 - Quaternary structure

More than one A dimer is the

Tetramer Hexamer
polypeptide most simple form
• Separate
subunits
• Can be the
same or else
different
Alcohol dehydrogenase – Asian Flush

Alcohol flush reaction is a condition in which an

individual develops flushes or blotches associated
with erythema on the face, neck, shoulders, and in
some cases, the entire body after
consuming alcoholic beverages.

The build-up of acetaldehyde is what causes blood

vessels to dilate and the face to turn red – the so-
called “Asian flush syndrome”.

Because of the association with Asian ancestry,

alcohol flush reaction has also been referred to by
such informal names as Asian flush
syndrome, Asian flush, and Asian glow.
Approximately 36% of East Asians (Japanese,
Chinese, and Koreans) show a characteristic
physiological response to drinking alcohol that
includes facial flushing,nausea, and tachycardia.[3]
Protein Structure & Disease
Protein Structure & Disease
Cystic Fibrosis

In the first half of the 1980s, scientists realized that malfunction of epithelial
tissue was at fault in every organ impaired by cystic fibrosis. (An epithelium is a
sheet of cells that forms a barrier between different compartments of the body;
such sheets, which often secrete mucus, line the intestines and many ducts.)

In particular, 2 avenues of investigation revealed that the epithelia of patients

with cystic fibrosis were relatively impermeable to chloride. This discovery
implied that some chloride-transporting channel in epithelial tissue was
malfunctioning.
Cystic Fibrosis – the gene is found!

• Lap-Chee Tsui and John R. Riordan of the Hospital for Sick Children in Toronto
and by Francis S. Collins, then at the University of Michigan and now the Director
of the Human Genome Project at NIH.
• Cystic fibrosis transmembrane conductance regulator (CFTR) gene.
• Abnormality in the DNA that appeared to account for about 70 percent of cystic
fibrosis cases  the AF508 mutation consists of the deletion of three nucleotides (
DNA building blocks) from the gene. That loss causes the protein product of the
gene to lack a single amino acid: phenylalanine at position 508.
Cystic Fibrosis – the gene is found!
CFTR – how it works..
Single-Gene Disorders

These disorders involve mutations in the DNA sequences of single genes. As a result,
the protein the gene codes for is either altered or missing.
Adenosine deaminase (ADA) deficiency
Alpha-1 Antitrypsin Deficiency
Cystic Fibrosis
Galactosemia
Huntington's Disease
Maple Syrup Urine Disease (MSUD)
Neurofibromatosis Type 1
Pachyonychia Congenita
Phenylketonuria
Severe Combined Immunodeficiency
Sickle Cell Disease
Smith-Lemli-Opitz Syndrome