Lecture 8

Lecture 8:

The 3D structure of proteins:

Primary and secondary structure

Campbell and Farrell: 4.1-4.3

http://www.pdfonline.com/easypdf/?gad=CLjUiqcCEgjbNejkqKEugRjG27j-AyCw_-AP

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’


The native 3D structure of a protein is determined by:

• the amino acid sequence

• the amino acid composition



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


Small changes in primary structure can have big effects:

• vasopressin vs. oxytocin

• SRY

• etc.


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’



:

:

+

+


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


Two main REGULAR conformations of the backbone:

1.-Helix

2. -Sheet


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



Factors that disrupt or destabilize an alpha helix


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


2. Repulsion between side-chains of like charges can ‘pull the helix apart’


3. Bulky side-chains (Val, Leu, Ile) located adjacent to one another can cause steric repulsion (i.e. crowding)


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


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



Beta sheets are often pleated


Irregularities (bulges) in beta sheets


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


‘Loops’, ‘random coil’ or ‘linker’elements connect secondary structure

elements


Supersecondary structures:

Combinations of secondary structures


Structural motifs (modules):

Repetitive supersecondary structures








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


Fibrous Proteins vs. Globular proteins


Education

Lecture 8