1. Protein Structure
Timothy G. Standish, Ph. D.

2. The Genetic Code U C A G U C A G S E C O N D B A S E F I R S T B A E T
Neutral Non-polar
Polar
Basic
Acidic
S E C O N D B A S E U C A G F I R S T B A E U
UUU
UUC
UUA
UUG
UCU
UCC
UCA
UCG
UAU
UAC
UAA
UAG
UGU
UGC
UGA
UGG U C A G T H I R D B A S E
Phe
Tyr
Cys
Ser
Stop
Leu
Stop
Trp C
CUU
CUC
CUA
CUG
CCU
CCC
CCA
CCG
CAU
CAC
CAA
CAG
CGU
CGC
CGA
CGG U C A G
His
Leu
Pro
Arg
Gln† A
AUU
AUC
AUA
AUG
ACU
ACC
ACA
ACG
AAU
AAC
AAA
AAG
AGU
AGC
AGA
AGG U C A G
Asn†
Ser
Ile
Thr
Lys
Arg
†Have amine
groups
Met/
start G
GUU
GUC
GUA
GUG
GCU
GCC
GCA
GCG
GAU
GAC
GAA
GAG
GGU
GGC
GGA
GGG U C A G
Asp
Val
Ala
Gly*
*Listed as
non-polar by
some texts
Glu

3. Different Amino Acid ClassesOH H O
H2N C
Alanine C OH H O HS
H2N
Cysteine
Non-polar
Polar OH O H
H2N C R
Generic
Acid
Amine C OH H O
H+N
H2N NH
Histidine H
H2N C O OH
Aspartic
acid ?
Acid
Basic

4. Non-Polar Amino Acids OH O H H2N C Glycine Methionine OH O H H2N C H3C
Valine OH O H
H2N C
H3C
CH3
Leucine OH O H
H2N C
H3C
CH3
Alanine OH H O
H2N C
Tryptophan OH O H
H2N C NH
Phenylalanine OH H O
H2N C
Isoleucine OH O H
H2N C
H3C
Proline OH O H
H2N+ C
H2C
CH2

5. Polar Amino Acids Tyrosine HO H O H2N C OH Serine OH O H H2N C HO CH3
Threonine OH O H
H2N C
Glutamine H
H2N C O OH
NH2
Cysteine C OH H O HS
H2N
Asparagine H
H2N C O OH
NH2

6. Acidic Amino Acids Aspartic Glutamic acid acid H2N H2N OH OH C C H H O

7. Basic Amino Acids O Histidine H2N OH O Lysine C H2N OH C O Arginine HNH
Lysine OH O H
H2N C
+H3N
Arginine OH O H
H2N C N
+H2N
NH2

8. Levels Of Protein Organization
Primary Structure - The sequence of amino acids in the protein
Secondary Structure - The formation of a helices and b pleated sheets due to hydrogen bonding between the peptide backbone
Tertiary Structure - Folding of helices and sheets influenced by R groups
Quaternary Structure - The association of more than one polypeptide into a protein complex influenced by R groups

9. Levels Of Protein Organization Primary Structure
Met-Gly-Ala-Pro-His-Ile-Asp-Glu-Met-Ser-Thr-...

10. Glyceraldehyde-3-Phosphate Dehydrogenase Primary Structure
The Mycoplasma genitalium G-3P dehydrogenase protein sequence:
MAAKNRTIKV AINGFGRIGR LVFRSLLSKA NVEVVAINDL TQPEVLAHLL KYDSAHGELK RKITVKQNIL QIDRKKVYVF SEKDPQNLPW DEHDIDVVIE STGRFVSEEG ASLHLKAGAK RVIISAPAKE KTIRTVVYNV NHKTISSDDK IISAASCTTN CLAPLVHVLE KNFGIVYGTM LTVHAYTADQ RLQDAPHNDL RRARAAAVNI VPTTTGAAKA IGLVVPEANG KLNGMSLRVP VLTGSIVELS VVLEKSPSVE QVNQAMKRFA SASFKYCEDP IVSSDVVSSE YGSIFDSKLT NIVEVDGMKL YKVYAWYDNE SSYVHQLVRV VSYCAKL

11. Protein Secondary Structure
The peptide backbone of DNA has areas of positive charge and negative charge
These areas can interact with one another to form hydrogen bonds
The result of these hydrogen bonds are two types of structures:
a helices
b pleated sheets

12. Protein Secondary Structure: a Helix+ - C O OH N H HO

13. Protein Secondary Structure: a Helix+ - C O OH N H HO

14. Protein Secondary Structure: a Helix
R groups stick out from the a helix influencing higher levels of protein organization

15. Yeast Cytochrome C Oxidase Subunit IV LeaderP L T C S I K F A M Q
Yeast Cytochrome C Oxidase Subunit IV Leader
First 12 residues are sufficient for transport to the mitochondria
Neutral Non-polar
Polar
Basic
Acidic
MLSLRQSIRFFKPATRTLCSSRYLL
This leader sequence probably forms an a helix
This would localize specific classes of amino acids in specific parts of the helix
There are about 3.6 amino acids per turn of the helix with a rise of 0.54 nm per turn

16. Protein Secondary Structure: b Pleated Sheet

17. Protein Secondary Structure: b Pleated Sheet

18. Levels Of Protein Organization Tertiary Structure
Tertiary structure results from the folding of a helices and b pleated sheets
Factors influencing tertiary structure include:
Hydrophobic/hydrophilic interactions
Hydrogen bonding
Disulfide linkages
Folding by chaperone proteins

19. G-3-P Dehydrogenase Tertiary Structure
Picture source: SWISS-PROT

20. Levels Of Protein Organization Quaternary Structure
Quaternary structure results from the interaction of independent polypeptide chains
Factors influencing quaternary structure include:
Hydrophobic/hydrophilic interactions
Hydrogen bonding
The shape and charge distribution on associating polypeptides

21. G-3-P Dehydrogenase from Bacillus stearothermophilus
Skarzynski, T., Moody, P. C. E., Wonacott, A. J.: Structure of Holo-Glyceraldehyde-3-Phosphate Dehydrogenase from Bacillus Stearothermophilus at 1.8 Angstroms Resolution. J.Mol.Biol. 193 pp. 171 (1987)
Picture source: SWISS-PROT

22. The Globin Gene Family a b
Globin genes code for the protein portion of hemoglobin
In adults, hemoglobin is made up of an iron containing heme molecule surrounded by 4 globin proteins: 2 a globins and 2 b globins a b Fe
During development, different globin genes are expressed which alter the oxygen affinity of embryonic and fetal hemoglobin

23. Haemoglobin
Luisi, B., Shibayama, N.: Structure of Haemoglobin in the Deoxy Quaternary State with Ligand Bound at the Alpha Haems. J.Mol.Biol. 206 pp. 723 (1989)
Picture source: SWISS-PROT

24. The
End