Transcript Introduction to Protein Structure and Its Prediction

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 acid
Hydrophobic: AVLIFPM
Charged residues: DEKR
Polar: STCNQHYW
Special : G
• Polypeptide chain
Extend from its amino terminus to
its carboxy terminus
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
How to Describe Protein Structure
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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
Antiparallel Beta Sheet
Parallel Beta Sheet
We can also have mix.
Secondary Structure : Loop Regions
Less conserved structure
– Insertions and deletions
are more often
– Conformations are flexile
Tertiary Structure
Phi – N -C bond
Psi – C-C’ bond
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 antiparallel 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
Up-and-down
barrels
Greek key
Jelly roll
Beta-Domain Structures
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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.