1. Introduction to Protein Structure
Rui Kuang

2. Why do we study protein structure
Protein – Derived from Greek word proteios meaning “of the first rank” in 1838 by Jöns J. Berzelius.
Crucial in all biological processes, such as Enzymatic catalysis, transport and storage, immune protection……
Functions depend on structures --- structure can help us to understand function

3. Building blocks Amino acid Polypeptide chain
Hydrophobic: AVLIFPM
Charged residues: DEKR
Polar: STCNQHYW
Special : G
Polypeptide chain
Extend from its amino terminus to its carboxy terminus

4. Special Amino Acids Glycine Side chain is –H, very flexible Proline
has two covalent bonds with backbone
Cysteine
can form disfulfide bridge to stabilize structure

5. How to Describe Protein Structure
Primary: amino acid sequence
Secondary structure: alpha helix, beta sheet and loops
Tertiary: Phi-Psi angle
Quaternary: arrangement of several polypeptide chains

6. Secondary Structure : Alpha Helix
hydrogen bonds between n and n+i (i=3,4,5)

7. Secondary Structure : Beta Sheet
Antiparallel Beta Sheet
Parallel Beta Sheet
We can also have mix.

8. Secondary Structure : Loop Regions
Less conserved structure
Insertions and deletions are more often
Conformations are flexile

9. Tertiary Structure
Phi – N bond
Psi – -C’ bond

10. Protein Domains
A polypeptide chain or a part of a polypeptide chain that can fold independently into a stable tertiary structure.
Built from different combinations of secondary structure elements and motifs

11. Three Main Classes of Domain Structures
During the evolution, the structural core tends to be conserved
Alpha domains : The core is build up exclusively from alpha helices
Beta domains : The core comprises anti-parallel beta sheets packed against each other
Alpha/Beta domains : a predominantly parallel Beta sheet surrounded by alpha helices

12. Alpha-Domain Structures
It’s coiled coil structure
The most common one is four-helix bundle but we can have large and complex ones.

13. Alpha-Domain Structures
Knobs in holes
Ridges in grooves

14. Beta-Domain Structures
The cores built up by four or five to ten beta strands
Beta strands are predominantly antiparallel
The three most frequently groups: up-and-down barrels, Greek keys, and jelly roll barrels
Parallel Beta-helix is an exeception

15. Beta-Domain Structures
Up-and-down
barrels
Greek key Jelly roll

16. Beta-Domain Structures
The most frequent domain structures
Barrel :beta-core surrounded by alpha-helix
Open twist :parallel or mixed beta with alpha on both sides
Horseshoe :Parrallel beta curve with alpha outside

17. Determination of Protein Structures
X-ray crystallography
The interaction of x-rays with electrons arranged in a crystal can produce electron-density map, which can be interpreted to an atomic model. Crystal is very hard to grow.
Nuclear magnetic resonance (NMR)
Some atomic nuclei have a magnetic spin. Probed the molecule by radio frequency and get the distances between atoms. Only applicable to small molecules.