Introduction to Protein Structure

Rui Kuang

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

Building blocks

• Amino acidHydrophobic: AVLIFPM

Charged residues: DEKR

Polar: STCNQHYW

Special : G

• Polypeptide chainExtend from its amino terminus to its carboxy terminus

Special Amino Acids

• GlycineSide chain is –H, very flexible

• Prolinehas two covalent bonds with backbone

• Cysteinecan form disfulfide bridge to stabilize structure

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

Secondary Structure : Alpha Helix

hydrogen bonds between n and n+i (i=3,4,5)

Secondary Structure : Beta Sheet

Parallel Beta SheetAntiparallel Beta Sheet

We can also have mix.

Secondary Structure : Loop Regions

Less conserved structure– Insertions and deletions

are more often– Conformations are flexile

Phi – N - bond

Psi – -C’ bond

Tertiary Structure

C

C

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

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

Alpha-Domain Structures• It’s coiled coil structure

• The most common one is four-helix bundle but we can have large and complex ones.

Alpha-Domain Structures• Knobs in holes

• Ridges in grooves

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

Beta-Domain Structures

Greek key Jelly rollUp-and-down

barrels

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

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.