Transcript Introduction to Protein Science Architecture, Function

Introduction to Protein
Science
Architecture, Function, and Genomics
Arthur M. Lesk
Chapter 2: Genomics and Proteomics
P47-51
2008-11-10
Jeong, Da-Geum, UST
Chapter2: Genomics and Proteomics - Protein evolution
Flow of Change-----------------------------
2.Amino acid or
1.Nucleic acid
expression pattern
of protein
Selected
advantage
3.Activity of the
Protein
Disadvantage
Exception: Silent mutation
Ex: 3rd position in exons,
untranslated regions
Simplest change to a protein is the substitution of a single amino acid
Then, what is the effect on the protein structure and function?
Chapter2: Genomics and Proteomics - Protein evolution
2. Change of the Structure(folding)
1.No noticeable effect
Ex) Hemoglobin b-chain mutation
-> Robust protein to mutation
B60Val-> Glu, - rapid degraded
Ex) enzymes in closely related species
B106Leu->Arg - precipitate
Substitution of (a single)
amino acid
3.Sensitive position in the active site
Ex) Gln-> Arg substitution,
Malate dehydrogenase ->
4. Easy to aggregate->
Very serious clinical consequence
Ex) Sickle cell anaemia, Z-mutant of a1-antitrypsin
Lactate dehydrogenase
Other type of
change
1 Insertion
2 Deletion – cystic fibrosis
3 Transpositions – degraded in the ER
Chapter2: Genomics and Proteomics - Protein evolution
How do proteins develop new functions?
(1) Divergence – progressive localized changes in sequence and structure
-> initially to change in specificity
-> ultimately to changes in the nature of the reaction catalysed
(2) Recruitment – one protein is adapted
(3)‘Mixing and matching’ of domains or modular evolution
- large-scale structural changes
- Individual domain-> gain of function, modified function, different processes.
Robustness of protein structure to mutations is
a maintenance of structure in spite of the divergence of sequences
during evolution