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Transcript
Protein Structure
Protein Functions
• Three examples of protein functions
Alcohol
dehydrogenase
oxidizes alcohols
to aldehydes or
ketones
– Catalysis:
Almost all chemical reactions in a living
cell are catalyzed by protein enzymes.
– Transport:
Some proteins transports various
substances, such as oxygen, ions, and so
on.
Haemoglobin
carries oxygen
– Information transfer:
For example, hormones.
Insulin controls
the amount of
sugar in the
blood
Amino acid: Basic unit of protein
R
NH3
+
C
Amino group
H
Different side chains, R,
determine the
COO properties of 20 amino
Carboxylic
acid group acids.
An amino acid
20 Amino acids
Glycine (G)
Alanine (A)
Valine (V)
Isoleucine (I)
Leucine (L)
Proline (P)
Methionine (M)
Phenylalanine (F)
Tryptophan (W)
Asparagine (N)
Glutamine (Q)
Serine (S)
Threonine (T)
Tyrosine (Y)
Cysteine (C)
Lysine (K)
Arginine (R)
Histidine (H)
Asparatic acid (D) Glutamic acid (E)
White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic
Each protein has a unique structure!
Amino acid sequence
NLKTEWPELVGKSVEEAK
KVILQDKPEAQIIVLPVGTI
VTMEYRIDRVRLFVDKLD
Folding!
Primary
Assembly
Secondary
Folding
Tertiary
Packing
Quaternary
Interaction
PROCESS
STRUCTURE
Protein Structure
Protein Assembly
• occurs at the ribosome
• involves polymerization of
amino acids attached to
tRNA
• yields primary structure
Primary Structure
primary structure of human insulin
CHAIN 1: GIVEQ CCTSI CSLYQ LENYC N
CHAIN 2: FVNQH LCGSH LVEAL YLVCG ERGFF YTPKT
•
•
•
•
linear
ordered
1 dimensional
sequence of amino acid
polymer
• by convention, written
from amino end to
carboxyl end
• a perfectly linear amino
acid polymer is neither
functional nor
energetically favorable 
folding!
Protein Folding
• occurs in the cytosol
• yields secondary structure
• involves localized spatial
interaction among primary
structure elements, i.e. the amino
acids
Secondary Structure
• non-linear
• 3 dimensional
• localized to regions of an
amino acid chain
• formed and stabilized by
hydrogen bonding,
electrostatic and van der
Waals interactions
Secondary structure
α-helix
β-sheet
Secondary structures, α-helix
and β-sheet, have regular
hydrogen-bonding patterns.
Protein Packing
• occurs in the cytosol (~60% bulk
water, ~40% water of hydration)
• involves interaction between
secondary structure elements
and solvent
• yields tertiary structure
Tertiary Structure
• non-linear
• 3 dimensional
Protein Interaction
• occurs in the cytosol, in close proximity to other folded and
packed proteins
• involves interaction among tertiary structure elements of
separate polymer chains
Quaternary Structure
• non-linear
• 3 dimensional
3D structure of proteins
Tertiary
structure
Quaternary structure
Class/Motif
• class = secondary structure
composition,
e.g. all , all , / , +
• motif = small, specific combinations of
secondary structure elements,
e.g. -- loop
• both subset of fold
/
Fold
• fold = architecture = the overall
shape and orientation of the
secondary structures, ignoring
connectivity between the
structures,
e.g. / barrel, TIM barrel
• subset of fold
families/superfamilies
Fold families/Superfamilies
• fold families = categorization that
takes into account topology and
previous subsets as well as
empirical/biological properties, e.g.
flavodoxin
• superfamilies = in addition to fold
families, includes
evolutionary/ancestral properties
CLASS: +
FOLD: sandwich
FOLD FAMILY: flavodoxin
Hierarchical nature of protein structure
Primary structure (Amino acid sequence)
↓
Secondary structure (α-helix, β-sheet)
↓
Tertiary structure (Three-dimensional structure
formed by assembly of secondary structures)
↓
Quaternary structure (Structure formed by more than
one polypeptide chains)
Protein structure and its function
Example of enzyme reaction
substrates
enzyme
A
enzyme
B
Matching
the shape
to A
enzyme
A
Binding to A
Digestion
of A!
Hormone receptor
Antibody
Protein structure prediction has remained
elusive over half a century
“Can we predict a protein structure from
its amino acid sequence?”
Now, impossible!
Summary
• Proteins are key players in our living systems.
• Proteins are polymers consisting of 20 kinds of amino acids.
• Each protein folds into a unique three-dimensional structure
defined by its amino acid sequence.
• Protein structure has a hierarchical nature.
• Protein structure is closely related to its function.
• Protein structure prediction is a grand challenge of
computational biology.