PROTEIN FORM AND FUNCTION

1
PROTEIN FORM AND FUNCTION PROTEIN EVOLUTION AT
THE SEQUENCE LEVEL
Sequence variation Gene/protein
families Extended proteins Domain shuffling
Partial gene duplication results in gene
elongation
2
HAPTOGLOBINS
a b chains S-S linked tend to form
oligomers (ab)2 etc. In humans a chain is
polymorphic aI (83
residues) aIF (Lys54) and aIS (Glu54)
aII (143
residues)
Partial gene duplication
Gene frequencies aIF 0.16
aIS 0.24
aII 0.60
3
PROPOSED MECHANISM FOR PARTIAL GENE DUPLICATION
OF HAPTOGLOBIN
4
OVOMUCOID
An egg white protein that binds/inhibits
proteases 3 domains, showing marked sequence and
3D similarity
I
II
III
protein
gene
Appears to have arisen by two rounds of partial
duplication. The two exons corresponding to each
domain are not similar
5
The 3 Domains of Ovomucoid
6
Immunoglobulin G
7
THE ELASTIN GENE
Cross link domains
Elastomeric domains
8
Preproenkephalins
9
ANTI-FREEZE PROTEIN
From Chen et al (1997)
10
PROTEIN FORM AND FUNCTION PROTEIN EVOLUTION AT
THE SEQUENCE LEVEL
Sequence variation Gene/protein
families Extended proteins Domain shuffling
11
EXON/DOMAIN SHUFFLING
Dehydrogenases Lactate dehydrogenase
(LDH) Malate dehydrogenase (MDH) Alcohol
dehydrogenase ADH) Glyceraldehyde phosphate
dehydrogenase (GAPDH) Glutamate
dehydrogenase Pyruvate dehydrogenase
12
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
13
DOMAINS IN DEHYDROGENASES
A1 and A2 - the NAD-binding domain
14
DOMAINS IN THE CLOTTING CASCADE ENZYMES
From Li Graur (2000)
F1, F2 fibronectin type 1 2 modules AP
apple module GA
gamma-carboxy EG EGF modules
KR kringle module
glutamate domain
15
CLOT LYSIS
tPA

• Plasmin
• a serine protease (trypsin like) which
  specifically breaks down fibrin
• formed from plasminogen (86K protein), by action
  of other proteases urokinase (kidney) or tissue
  plasminogen activator (tPA)

From Stryer
16
A model showing how L1 retrotransposition can
generate genomic diversity
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REPETITIVE ELEMENTS
Repetitive elements in the human genome - Li et
al. (2001) SINES 12.5
(Alu 10.7) LINES 18.9
(L1 15.4) DNA transposons 2.7 LTR
elements 7.9 Other
0.1
42.1 Including duplicative transposons?
SINE short interspersed repetitive
element LINE long interspersed repetitive
element LTR long terminal repeat