1. CHMI 2227E Biochemistry I Proteins: Secondary Structure
Beta Strands and Beta Sheets
Loops and Turns
A special case: Collagen
CHMI E.R. Gauthier, Ph.D.

2. Beta Strands and Beta Sheets
The other common secondary structure is called the β structure which includes β strands and β sheets
β strands are portions of the polypeptide chain that are almost fully extended having a “zig-zag” shape
β strands are flexible but not elastic
CHMI E.R. Gauthier, Ph.D.

3. Beta Sheets
When multiple β strands are arranged side-by-side, they form β sheets;
Proteins rarely contain isolated β strands because the structure by itself is not significantly more stable than other conformations
However, β sheets are stabilized by hydrogen bonds between carbonyl oxygens and amide hydrogens on adjacent β strands.
CHMI E.R. Gauthier, Ph.D.

4. Hydrogen Bonded Beta Strands
The H-bonded β strands can be on separate polypeptide chains or on different segments of the same chain
The β strands in a sheet can be either parallel (running in the same N- to C- terminal direction) or antiparallel (running in opposite N- to C- terminal direction) N C N C N C C N
CHMI E.R. Gauthier, Ph.D.

5. Antiparallel Beta Strands
The hydrogen bonds are nearly perpendicular to the extended polypeptide chains
The carbonyl oxygen and the amide hydrogen atoms of one residue form hydrogen bonds with the amide hydrogen and carbonyl oxygen of a single residue in the other strand
CHMI E.R. Gauthier, Ph.D.

6. Parallel Beta Strands
In the parallel arrangement, the hydrogen bonds are not perpendicular to the extended chains, and each residue forms hydrogen bonds with the carbonyl and amide groups of two different residues on the adjacent strand
CHMI E.R. Gauthier, Ph.D.

7. Mixed Beta Sheets
Many strands, typically 4 or 5 but as many as 10 or more, can come together in β sheets. Such sheets can be purely antiparallel, purely parallel, or mixed
CHMI E.R. Gauthier, Ph.D.

8. Beta Sheet Conformation
The R groups from the amino acids point alternatively above and below the plane of the sheet
CHMI E.R. Gauthier, Ph.D.

9. Beta Pleated Sheets
Beta Pleated Sheets: Silk
In certain proteins adopting a β conformation, small R groups from amino acids such as Ala, Gly and Ser allow the β sheets to stack closely together;
This β conformation is responsible for the flexible characteristic of the silk filaments
Example: Silk Fibroin
CHMI E.R. Gauthier, Ph.D.

10. Loops and Turns
In an α-helix or a β strand, consecutive residues have a similar conformation that is repeated throughout the structure;
Most of these regions of secondary structures can be characterized as loops and turns since they cause directional changes in the polypeptide backbone;
CHMI E.R. Gauthier, Ph.D.

11. Loops and Turns
Loops and turns connect α-helices and β strands and allow the polypeptide chain to fold back on itself, producing the compact 3D shape seen in native structures;
Loops often contain hydrophilic residues and are usually found on the surfaces of proteins where they are exposed to solvent and form H-bonds with water
CHMI E.R. Gauthier, Ph.D.

12. Loops and Turns
Loops containing only a few (up to 5) residues are referred to as turns if they cause an abrupt change in the direction of a polypeptide change;
The most common types of tight turns are called reverse turns or β turns because they usually connect different antiparallel β strands
CHMI E.R. Gauthier, Ph.D.

13. Beta turns
β turns contain 4 amino acid residues and are stabilized by hydrogen bonding between the carbonyl oxygen of the first residue and the amide hydrogen of the fourth residue;
β turns produce an abrupt (usually about 180°) change in the direction of the polypeptide chain
Gly and Pro are often part of the β turns
Pro is capable of forming a cis peptide bond conformation which is highly susceptible in forming β turns
Glycine has a small R group which is capable of generating unique psi and phi angles permitting a high degree of flexibility
CHMI E.R. Gauthier, Ph.D.

14. A special case : collagen
Family of over 20 rod-like proteins;
Important part of connective tissue (1/3 of all proteins in mammals);
Classified into 5 different types, according their amino acid content, their primary structure and their sugar content.
Type I
bone, tendon, fibrocartilage, dermis, cornea
Type II
nucleus pulposus, hyaline cartilage
Type III
intestinal and uterine wall
Type IV
endothelial, epithelial membranes
Type V*
cornea, placenta, bone, heart valve
* Found in small quantities
CHMI E.R. Gauthier, Ph.D.

15. A special case : collagen
Chain 1
Chain 2
Chain 3
Consists in a triple helix: 3 polypeptide chains (each left handed) are intertwined together to form a right-handed superhelix;
For each left-handed helix:
Pitch: 0.94 nm
Rise: 0.31 nm per residue
3 residues per turn
1000 residues per chain
So: the collagen helix is more extended than the a-helix
(from Kadler, 1996)
Triple helix
CHMI E.R. Gauthier, Ph.D.

16. A special case : collagen Type V collagen = 1839 a.a.!!
CHMI E.R. Gauthier, Ph.D.

17. A special case : collagen
Hypro
5-Hylys
The collagen polypeptides have a very specific amino acid composition:
1/3 Gly
1/4 Pro
1/4 Hypro (hydroxyproline) and 5-Hylys (hydroxylysine)
These residues follow a strict sequence where Gly is always repeated every third position – WHY??;
CHMI E.R. Gauthier, Ph.D.

18. A special case : collagen13
CHMI E.R. Gauthier, Ph.D.

19. A special case : collagen
The presence of Gly at every third residue allows each collagen chains to form a tightly wound helix that can accommodate Pro/Hypro (which are otherwise rarely included in helices);
Since the helix has 3 a.a. per turn, having Gly at every third residue means that Gly is always on the same side of the helix;
It just so happens that Gly is always positioned at the center of the triple helix;
This allows close packing of the three helices, which can interact and yield a very strong, rope-like structure.
CHMI E.R. Gauthier, Ph.D.

20. Hydrogen bonds stabilize the collagen triple helix
Gly of Chain 1
Pro of Chain 2 G
Glycine
Hypro
Pro
CHMI E.R. Gauthier, Ph.D.

21. Formation of collagen fibers
Collagen triple helix
(tropocollagen)
Lysine
CHMI E.R. Gauthier, Ph.D.

22. Formation of collagen fibers
Transmission electron
microscopy of collagen
fibers
CHMI E.R. Gauthier, Ph.D.

23. Collagen, Vitamin C and scurvy
The formation of Hypro requires the enzymatic modification of Pro in a reaction which involves:
Prolyl hydroxylase (an enzyme)
Fe+2
Ascorbic acid, a derivative of Vit C and an antioxidant, keeps iron in its reduced Fe+2 form, and not the oxidized, more stable Fe+3 form.
Humans cannot make Vit C on their own;
In the absence of Vit C, the collagen triple helix cannot assemble properly, leading to a much softer connective tissue.
CHMI E.R. Gauthier, Ph.D.