lecture 8
DESCRIPTION
BIC1B Lecture 8TRANSCRIPT
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Lecture 8:
The 3D structure of proteins:
Primary and secondary structure
Campbell and Farrell: 4.1-4.3
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Proteins are made up of long chains of amino acids (>100)
The 3D structure of a protein is critical to its function
The functional 3D structure of a protein is called the ‘native
conformation’
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The native 3D structure of a protein is determined by:
• the amino acid sequence
• the amino acid composition
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Primary structure: the order of amino acids in the protein
N-ALA-PRO-SER-ARG-LYS-PHE-PHE-VAL-GLY-GLY-ASN-TRP-LYS--MET-ASN-GLY-ARG-LYS-GLN-SER-LEU-GLY-GLU-LEU-ILE-GLY--THR-LEU-ASN-ALA-ALA-LYS-VAL-PRO-ALA-ASP-THR-GLU-VAL--VAL-CYS-ALA-PRO-PRO-THR-ALA-TYR-ILE-ASP-PHE-ALA-ARG--GLN-LYS-LEU-ASP-PRO-LYS-ILE-ALA-VAL-ALA-ALA-GLN-ASN--CYS-TYR-LYS-VAL-THR-ASN-GLY-ALA-PHE-THR-GLY-GLU-ILE--SER-PRO-GLY-MET-ILE-LYS-ASP-CYS-GLY-ALA-THR-TRP-VAL--VAL-LEU-GLY-HIS-SER-GLU-ARG-ARG-HIS-VAL-PHE-GLY-GLU--SER-ASP-GLU-LEU-ILE-GLY-GLN-LYS-VAL-ALA-HIS-ALA-LEU--ALA-GLU-GLY-LEU-GLY-VAL-ILE-ALA-CYS-ILE-GLY-GLU-LYS--LEU-ASP-GLU-ARG-GLU-ALA-GLY-ILE-THR-GLU-LYS-VAL-VAL--PHE-GLU-GLN-THR-LYS-VAL-ILE-ALA-ASP-ASN-VAL-LYS-ASP--TRP-SER-LYS-VAL-VAL-LEU-ALA-TYR-GLU-PRO-VAL-TRP-ALA--ILE-GLY-THR-GLY-LYS-THR-ALA-THR-PRO-GLN-GLN-ALA-GLN--GLU-VAL-HIS-GLU-LYS-LEU-ARG-GLY-TRP-LEU-LYS-SER-ASN--VAL-SER-ASP-ALA-VAL-ALA-GLN-SER-THR-ARG-ILE-ILE-TYR--GLY-GLY-SER-VAL-THR-GLY-ALA-THR-CYS-LYS-GLU-LEU-ALA--SER-GLN-PRO-ASP-VAL-ASP-GLY-PHE-LEU-VAL-GLY-GLY-ALA--SER-LEU-LYS-PRO-GLU-PHE-VAL-ASP-ILE-ILE-ASN-ALA-LYS--GLN---ALA-PRO-SER-ARG-LYS-PHE-PHE-VAL-GLY-GLY-ASN-TRP-LYS--MET-ASN-GLY-ARG-LYS-GLN-SER-LEU-GLY-GLU-LEU-ILE-GLY--THR-LEU-ASN-ALA-ALA-LYS-VAL-PRO-ALA-ASP-THR-GLU-VAL--VAL-CYS-ALA-PRO-PRO-THR-ALA-TYR-ILE-ASP-PHE-ALA-ARG--GLN-LYS-LEU-ASP-PRO-LYS-ILE-ALA-VAL-ALA-ALA-GLN-ASN--CYS-TYR-LYS-VAL-THR-ASN-GLY-ALA-PHE-THR-GLY-GLU-ILE--SER-PRO-GLY-MET-ILE-LYS-ASP-CYS-GLY-ALA-THR-TRP-VAL--VAL-LEU-GLY-HIS-SER-GLU-ARG-ARG-HIS-VAL-PHE-GLY-GLU--SER-ASP-GLU-LEU-ILE-GLY-GLN-LYS-VAL-ALA-HIS-ALA-LEU--ALA-GLU-GLY-LEU-GLY-VAL-ILE-ALA-CYS-ILE-GLY-GLU-LYS--LEU-ASP-GLU-ARG-GLU-ALA-GLY-ILE-THR-GLU-LYS-VAL-VAL--PHE-GLU-GLN-THR-LYS-VAL-ILE-ALA-ASP-ASN-VAL-LYS-ASP--TRP-SER-LYS-VAL-VAL-LEU-ALA-TYR-GLU-PRO-VAL-TRP-ALA--ILE-GLY-THR-GLY-LYS-THR-ALA-THR-PRO-GLN-GLN-ALA-GLN--GLU-VAL-HIS-GLU-LYS-LEU-ARG-GLY-TRP-LEU-LYS-SER-ASN--VAL-SER-ASP-ALA-VAL-ALA-GLN-SER-THR-ARG-ILE-ILE-TYR--GLY-GLY-SER-VAL-THR-GLY-ALA-THR-CYS-LYS-GLU-LEU-ALA--SER-GLN-PRO-ASP-VAL-ASP-GLY-PHE-LEU-VAL-GLY-GLY-ALA--SER-LEU-LYS-PRO-GLU-PHE-VAL-ASP-ILE-ILE-ASN-ALA-LYS—GLN-C
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Small changes in primary structure can have big effects:
• vasopressin vs. oxytocin
• SRY
• etc.
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The ‘backbone’ of a protein
The backbone can be thought of as the part of the polypeptide that ‘carries’ the side-chains
The backbone is sometimes called the ‘main chain’
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Secondary structure refers to the way that amide planes in the
backbone twist in order to allow optimal hydrogen bond formation
Regular secondary structure: Irregular secondary structure:
The H-bonding pattern is repetitive
The H-bonding pattern is not
repetitive
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Two main REGULAR conformations of the backbone:
1.-Helix
2. -Sheet
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Side-chain (R-group)
-carbon
1. ALPHA HELIX
12
34
56
7
8 Hydrogen bond is between C-O group on
residue n and N-H group of residue n + 3
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Factors that disrupt or destabilize an alpha helix
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1. Proline can’t be in an alpha helix
Fig. 3-4a, p. 71
1. Proline causes a kink in the protein backbone
2. Proline does not contain a backbone NH that can participate in hydrogen bonding
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2. Repulsion between side-chains of like charges can ‘pull the helix apart’
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3. Bulky side-chains (Val, Leu, Ile) located adjacent to one another can cause steric repulsion (i.e. crowding)
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Other helical secondary structures
310 helix
27 helix
4.416 helix
n
Residues per turn
Number of atoms connected in ‘ring’ by formation of H-bonds
Alpha 310 4.416
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1. BETA SHEET
The backbone is in an extendedconformation
H-bonding occurs between:
a) Sections of a main chain that doubles back on itself
(intrachain bonds)
b) Two different polypeptide main chains (interchain
bonds)
Beta strand
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Beta sheets are often pleated
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Irregularities (bulges) in beta sheets
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Reverse turns between the strands of a beta sheet
Type I: R-group 3 outside loop
Type II: R-group 3 inside loop
Type II with a Pro
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‘Loops’, ‘random coil’ or ‘linker’elements connect secondary structure
elements
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Supersecondary structures:
Combinations of secondary structures
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Structural motifs (modules):
Repetitive supersecondary structures
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Structural motifs (modules):
Repetitive supersecondary structures
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Structural motifs (modules):
Repetitive supersecondary structures
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Fig. 4-11, p. 97
Triple Helix
- Collagen consists of 3 polypeptide chains wrapped around one another
- Each chain consists of repeating units of
X – Pro – Gly or X – Hyp – Gly
X = any amino acid
Hyp = hydroxyproline
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Fibrous Proteins vs. Globular proteins