introduction to protein structure rui kuang. why do we study protein structure protein – derived...
TRANSCRIPT
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.