1. Outline What is an amino acid / protein
20 naturally occurring amino acids
Codon – triplet coding for an amino acid
How are proteins synthesized
Transcription & translation
DNA, chromosomes and base-pairing
Genes, intron and exons
Reading frames

2. Amino Acids
Functional group
Amine and carboxyl groups. Sidechain ‘R’ is attached to C-alpha carbon
The amino acids found in Living organisms are L-amino acids.

3. Amino Acids - peptide bond
Send around a model of a di-peptide
N-terminal
C-terminal

4. Examples of protein 3D-structure
Human proteins typically has a length of 220aa
Small protein
one domain
Bigger protein
two domains

5. The 20 amino acids Thr (T) Phe (F) Val (V) Ala (A) His (H) Arg (R)
Ser (S)
Leu (L)
Cys (C)
Met (M)
Asp (D)
Lys (K)
Asn (N)
Ile (I)
Trp (W)
Gln (Q)
Glu (E)
Tyr (Y)
Pro (P)
Gly (G)

6. Sidechain determines physical property
Positive charged (basic)
amino acids are: R, K, H
Negative (acidic): D and E
Arg - R
Lys - K
Asp - D
Glu - E
What is the charge ?
R,K (+) at physiological pH
D,E (-) at physiological pH
H sometimes (+) at physiological pH
These amino acids are also polar
His - H

7. Livingstone & Barton, CABIOS, 9, 745-756, 1993
Amino acid
Amino Acids
A – Ala
C – Cys
D – Asp
E – Glu
F – Phe
G – Gly
H – His
I – Ile
K – Lys
L – Leu
M – Met
N – Asn
P – Pro
Q – Gln
R – Arg
S – Ser
T – Thr
V – Val
W – Trp
Y - Tyr
What is the charge ?
R,K (+) at physiological pH
D,E (-) at physiological pH
H sometimes (+) at physiological pH
These amino acids are also polar
Livingstone & Barton, CABIOS, 9, , 1993

8. tRNA – amino acids and codons
Anti-codon
Codon for Phenylalanine is TTC

9. Transcription & translation
DNA
| Transcription
mRNA
| Translation
Protein
movie
In higher organisms the
picture is a bit more complex.
DNA -> pre-mRNA -> mRNA
->protein
Protein might need a chaperone
in order to fold correctly.

10. DNA - a double helix 5’ - A T T G C C - 3’ 3’ - T A A C G G - 5’
Many organelles in a cell:
Mention: Nucleus, cytoplasma, membrane, ER
James Watson and Francis Crick with their model
of the structure of the DNA molecule, 1953
5’ - A T T G C C - 3’
3’ - T A A C G G - 5’

11. DNA - Base pairing of nucleotides
T in DNA is replaced by U (Uracil) in RNA
-CH3 group in Thymine replaced with an -H in Uracil

12. Genes, chromosomes and base pairs
Genes are located at the chromosomes
bp in human genome - diploid => bp
Many organelles in a cell:
Mention: Nucleus, cytoplasma, membrane, ER

13. Gene structure - start stop and UTR
A gene starts in 5’ end with ATG - stop in 3’ end with TAG stop codon
Introns are spliced out from DNA transcript => mRNA
Transcript – piece
of DNA that is
transcribed into RNA i.e.
introns are spliced out
mRNA with
UTR-regions

14. ARTN_HUMAN chr1:

15. Single Nucleotide Polymorphism SNP
SNPs can be located anywere in the genome
non synomous (nsSNP) i.e. amino acid is changed
Synomous SNP does not affect the the protein
An amino acid is coded by 3 nucleotides
Leu: TTG

16. RNA/DNA translation table - codon

17. Identify possible start codons how many ?
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGCAGCTAACCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGGTAATGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGGTAATGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG

18. Identify possible start codons how many ?
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGCAGCTAACCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGGTAATGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGGTAATGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG

19. Reding frame
An open reading frame (orf) is a piece of DNA from start to stop
ATG (start codon) -> TAG or TGA or TAA (stop codons)
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGCAGCTAACCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGTAAGTGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG
Does the gene stop at that TAG ?
ATG CCA TGC ATA GCC CCT GCC ATA TCT ...
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGCAGCTAACCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGTAAGTGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG

20. Reding frame - II GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGCAGCTAACCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGTAAGTGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG
ATG CCA TGC ATA GCC CCT GCC ATA TCT ...
What is the result of translating the mRNA
into protein ? (only first 9 codons – use handout)
ATG CCA TGC ATA GCC CCT GCC ATA TCT ...
M P S I A P A I S

21. Forward and reverse strand
GATAATGGGGCATTCAGTACAAAAATCCCGTACGGAGCTA
GGCAGCTAACCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCATGGTAAGTGCCATGGTATAGCA
TGATAATGGGGCATTCAGTACAAAAATCCCGTACGTAGCT
GGTAGCTAGCCCGATGCCATGCATAGCCCCTGCCATATCT
TTCGATCATTCATTGTCAGTGGGTAAGTGCCATGGTATAG
5’-ATGCCATGCATAGCCC-3’ (forward or plus strand)
3’-TACGGTACGTATCGGG-5’ (reverse or negative strand)

22. Reading frame and reverse complement
Having a piece of DNA like:
TGCCATGCATAGCCCCTGCCATATCT
Forward strings & reading frames
1 : TGCCATGCATAGCCCCTGCCATATCT
2 : GCCATGCATAGCCCCTGCCATATCT
3 : CCATGCATAGCCCCTGCCATATCT
Reverse complement strings & reading frames
-1: TCTATACCGTCCCCGATACGTACCGT
-2: CTATACCGTCCCCGATACGTACCGT
-3: TATACCGTCCCCGATACGTACCGT

23. Summary - protein 20 naturally occurring amino acids L-amino acids
Amino acid is defined by a codon
One and three letter codes (important)
Protein reads from N -> C terminal

24. Summary – DNA/RNA transcription translation
DNA -> mRNA -> Protein
DNA: A-T, C-G
RNA: A-U, C-G
DNA/RNA strand reads from 5’ -> 3’
Gene starts with ATG until stop codon
64 codons, but only 20 amino acids

25. Subcellular location An animal cell: Many organelles in a cell:
Mention: Nucleus, cytoplasma, membrane, ER

26. Proteins - where are they found
Proteins are found in all living organisms
In humans there are approx proteins
Each protein has a specific function
Making up the human tissue - skin, hair, heart ...
Degrading the food we eat
Immune system
Transportation of Oxygen in blood
Triggering the growth of cells
The brain - neural signalling
Typically a protein is approx 220 aa in human
Proteins talk, i.e. Protein-protein interactions
To relay a signal across the cell-membrane

27. 1 and 3-letter codes There are 20 naturally occurring amino acids
Normally the one/three codes are used
Met - M
Asn - N
Pro - P
Gln - Q
Arg - R
Ser - S
Thr - T
Val - V
Trp - W
Tyr - Y
Ala - A
Cys - C
Asp - D
Glu - E
Phe - F
Gly - G
His - H
Ile - I
Lys - K
Leu - L

28. Graphic stick representation Different aa, different property
Ile - Hydrophobic
Phe - Hydrophobic & aromatic
How many carbons are there in the Ile aa ? Ans: 6
Are they L-amino acids ? Ans: Yes

29. The 20 amino acids
Just an overview - picture trying to show that the C-alpha atom is chiral

30. Charged amino acids (sidechain in red)
Arg - R
Lys - K
Asp - D
Glu - E
What is the charge ?
R,K (+) at physiological pH
D,E (-) at physiological pH
H sometimes (+) at physiological pH
These amino acids are also polar
His - H

31. Neutral amino acids Ile - I Leu - L Met - M Phe - F Pro - P
Property ?:
I - neutral, L - neutral, M - neutral, F - neutral, P - neutral
Pro - P

32. Property of amino acids (I) neutral, polar or charged ?
Ala - A
Asn - N
Cys - C
Gln - Q
Property ?:
A - neutral, N - polar C - slightly ploar, Q - polar, G - neutral
Gly - G

33. Property of amino acids (II) neutral, polar or charged ?
Ser - S
Thr - T
Trp - W
Tyr - Y
Property ?:
S - polar, T - polar W - slightly ploar, Y - neutral, V - neutral
Val - V

34. Protein structure Primary structure: Amino acids sequences
Secondary structure: Helix/Beta sheet
Tertiary structure: Fold, 3D cordinates

35. Protein structure -helix
helix 3 residues/turn - few, but not uncommon
-helix 3.6 residues/turn - by far the most common helix
Pi-helix 4.1 residues/turn - very rare

36. Protein structure strand/sheet

37. Protein structure
Ribbon representation - easy to see the secondary structure elements

38. Protein structure Too many atoms - information is lost
However notice proteins are surrounded by by water

39. Protein structure Hydrophilic/hydrophobic & stacking

40. Protein folds Class 4’th is ‘few secondary structure Architecture
Overall shape of a domain
Topology
Share secondary structure connectivity

41. Summary transcription translation DNA -> mRNA -> Protein
20 naturally occurring amino acids
Each amino acid has different properties, but can be grouped into:
Charged, neutral, polar (basic, acidic)
Secondary structure
-helix & -strand/-sheet
Protein hydrophobic inside, polar on the outside
Folds or classes: all , all , +, few secondar structure elements

42. Summary The amino acids
Ala
M -
Met
N -
Asn
C -
Cys
P -
Pro
D -
Asp
Q -
Gln
E -
Glu
R -
Arg
F -
Phe
S -
Ser
G -
Gly
H -
His
T -
Thr
I -
Ile
V -
Val
K -
Lys
W -
Trp
L -
Leu
Y -
Tyr