PROTEINS
Main Ideas p121-140
•Proteins are amino acids linked together by peptide bonds
•Dehydration synthesis
•Primary structure
•Conformation of least energy
•α-helix, β-sheet, helix-loop-helix e.g.
•May have unstructured areas in between.
•Secondary structure
•Domains
•Quaternary structure
The central dogma of biology
What are the structural levels of organization of proteins?
a polypeptide chain
The linear sequence of AA’s in a protein constitutes the primary structure
of the protein
Figure 4-2 Essential Cell Biology (© Garland Science 2010)
Remember: All 20 amino acids have a similar structure
Aspartate
Isoleucine
How amino acids
interact with water
Secondary
Structures
tertiary structure
(A) Cytochrome b562, a single-domain protein involved in electron transport in mitochondria. (B) the NAD-binding domain of the enzyme lactic dehydrogenase (C) the variable domain of an antibody
from the drawings of Jane Richardson
Tertiary structures are diverse
Proteins made of more than one polypeptide subunit also have quaternary structure
Hemoglobin
Figure 4-26 Essential Cell Biology (© Garland Science 2010)
The shape of extracellular proteins is often stabilized by disulfide bonds
Four Levels of Protein Structure
Four Levels of Protein Structure
& bonds that contribute to the structures
Four Levels of Protein Structure
& bonds that contribute to the structures
Four Levels of Protein Structure
& bonds that contribute to the structures
Four Levels of Protein Structure
& bonds that contribute to the structures
What specifies the correct structure of a protein?
What specifies the correct structure of a protein?
How do we know that a “correct” structure exists?
Figure 4-5 Essential Cell Biology (© Garland Science 2010)
This is reversible!
Denaturation by adding: 8M Urea to disrupt H2 bond and solvate hydrophobic side chains
β-Mercaptoethanol to disrupt disulfide bonds
What can we conclude?
Main Ideas p141-167
•coenzyme and cofactor
•Retinal
•Heme
•enzymatic pathway regulation
•allosteric or conformational changes
•prevent toxic buildup by regulating the beginning of a pathway
•kinases, GTP binding proteins, protein complexes and proteolysis
•Techniques
Molecular Chaperons
Even a single change in the primary structure can alter the function of the protein
Soluble, normal form
of a prion protein
Insoluble, abnormal form
Soluble, normal form
of a prion protein
Stanley Prusiner
Nobel Prize, 1997
Prion: proteinaceous infectious particle
Responsible for transmissable spongiform encephalopathies such as scrapie (sheep), kuru (cannibalistic tribe of New Guinea), Creutzfeld-Jakob disease (CJD), bovine spongiform encephalopathy (BSE, “mad cow disease”)
The abnormal form of the protein converts the normal protein to the abnormal form!
Scale bar, 50 µm. Photomicrographs from S. DeArmond
How would you regulate this pathway?
1 2 3 4 5
A B C D E F
6 7
G H
Enzyme 1 catalyzes the conversion of substrate A into Product B
Enzyme 2 catalyzes the conversion of substrate B into Product C
Enzyme 3 catalyzes the conversion of substrate C into Product D
Enzyme 4 catalyzes the conversion of substrate D into Product E
Enzyme 5 catalyzes the conversion of substrate E into Product F
Enzyme 6 catalyzes the conversion of substrate D into Product G
Enzyme 7 catalyzes the conversion of substrate G into Product H
How would you regulate this pathway?
1 2 3 4 5
A B C D E F
6 7
G H
Product F inhibits enzyme 4
Product H inhibits enzyme 6
Product D inhibits enzyme 1