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Operone lac
Principles of protein structure
and function
• Function is derived from structure
• Structure is derived from amino acid sequence
• Different activities and shapes of proteins due
to different amino acid sequences
Four levels of protein structure
Primary: amino acid sequence
Four levels of protein structure
Primary: amino acid sequence
Secondary: regular, repeated coiling
and folding of
polypeptide backbone
Four levels of protein structure
Primary: amino acid sequence
Secondary: regular, repeated coiling and
folding of polypeptide backbone
Tertiary: complete three-dimensional structure
Quaternary: arrangement of
subunits (in multisubunit
protein)
Secondary structure
• Regular, repeated coiling and folding of
polypeptide backbone
• Due to hydrogen bonding
• Two patterns
–  (alpha) helix
–  (beta) sheet
Tertiary
• Complete three-dimensional structure
• Due to weak interactions between side (R)
groups as well as covalent disulfide bonds
Weak interactions
Hydrogen bonds
Electrostatic interactions (ionic bonds)
Hydrophobic interactions
Van der Waals interactions
Tertiary
structure
formed
through side
chain
interactions
Hydrophobic interactions
Tertiary
• Complete three-dimensional structure
• Composed of:
– Motifs: specific combinations of secondary
structural elements
– Domains: structurally independent units
Motifs
specific
combinations of
secondary
structural
elements
Domains
Structurally
independent units
Two different
binding domains
to bind two
different
molecules
Tertiary
• Complete three-dimensional structure
Native conformation: functional structure
Most stable conformation
Tertiary
Fibrous Proteins = extended filaments
or
Globular proteins =
compact folded structure
Protein Folding
• Forming polypeptide chain requires energy
and information (template)
Protein Folding
• Forming polypeptide chain requires energy
and information (template)
• Forming native conformation requires NO
additional energy or information
(SELF ASSEMBLY)
Protein folding
Amino acid sequence contains all information
necessary for folding into a specific threedimensional structure
Protein Folding
Protein Folding
Many proteins fold by Assisted Self
Assembly
Correct assembly (native conformation)
requires assistance
by CHAPERONES
Protein unfolding = Denaturation
Loss of structure and function
–
–
–
–
Heat
Extreme pH
Detergents
Urea
Protein unfolding = Denaturation
Why do these conditions cause loss of
structure and function?
–
–
–
–
Heat
Extreme pH
Detergents
Urea
Tertiary
• Complete three-dimensional structure
• Due to weak interactions between side (R)
groups as well as covalent disulfide bonds
Lysozyme
Lysozyme
Tertiary: complete three-dimensional structure
Quaternary: arrangement of subunits
(in multisubunit protein)
Folding dell’emoglobina
Ribbon diagram
Hemoglobin
Quaternary structure
• Held together by weak interactions
between side (R/functional) groups as
well as covalent disulfide bonds
Structure-function relationship
• Function is derived from structure
• Structure is derived from sequence
Sickle-cell disease
Normal red blood cells Sickle shaped red blood cells
Due to single amino acid change in hemoglobin
= protein carries oxygen in red blood cells
Sickle-cell disease
Sickle-cell disease
• Single specific amino acid change causes
change in protein structure and solubility
• Results in change in cell shape
• Causes cells to clog blood vessels
Structure-function relationship
• Function is derived from structure
• Structure is derived from sequence
• Molecules with similar shapes can interact in
similar ways.
– For example, morphine, heroin, and other opiate drugs
are similar enough in shape that they can bind to the
same receptors as natural signal molecules, called
endorphins.
– Binding to
the receptors
produces
euphoria
and relieves
pain.
Fig. 2.19
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Structure-function relationship
• Function is derived from structure
• Structure is derived from sequence
› Similar sequences have similar functions
Structure-function relationship
• Function is derived from structure
• Structure is derived from sequence
› Similar sequences have similar functions
› Similar function often implies evolutionary
relatedness (homology)
» Sequence similarity suggests common
evolutionary origin
Homologous proteins
• Similar sequence
• Similar structure
• Similar function
• Evolved from common ancestor
• Belong to protein family
Proteins
Protein modification and degradation
1. Covalent chemical modification
2. Proteolytic processing and protein splicing
3. Proteolytic degradation
Reading and questions
• Chapter 3
• Questions
3-1, 3-2, 3-8, 3-11a, 3-15a -15d -15e, 3-16