Download Protein Secondary Structure

Protein Secondary Structure
Reading: Berg, Tymoczko & Stryer, 6th ed., Chapter 2, pp. 37-45
Problems in textbook: chapter 2, pp. 63-64, #1,5,9
Directory of Jmol structures of proteins:
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/routines/routines.html
Basic Jmol structure of the  helix:
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha/alpha.html
Jmol routine showing lots of views of  helix & 2 other kinds of helices:
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/helices/helices.html
Jmol structures of some -helical proteins
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha_domain/alpha_domain.html
Jmol structures of  barrel and  clam proteins
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/beta_domain/beta_domain.html
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Key Concepts
• Proteins: secondary structure
– major types of secondary structure found in many
proteins:
 helix
 conformation
 turns
– surface loops: not really secondary structure because
not regular, repetitive
– Unusual secondary structures - examples:
• collagen helix (found in collagen) (not covered in this
course)
• other kinds of helices, e.g. pi helix and 310 helix
(not covered in this course)
• Secondary structures are stabilized by all kinds of
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noncovalent bonds, but especially by hydrogen bonds.
Protein Secondary Structure
• Local, regular/recognizable conformations observed for
parts of the peptide backbone of a protein
• Examples:
–
 helix
 conformation
 turns
collagen helix
• Properties of peptide bond & hydrogen bonds --> 2° structures
–peptide bonds
• planarity
• adjacent planes related in space by set of 2 dihedral
angles for each amino acid residue
–hydrogen bonds
• Strongest are linear.
• Protein functional groups capable of H-bonding tend to do so
to maximum possible extent.
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• protein backbone amide groups (amide C=O: ---- H–N)
Review: 4 successive planar peptide groups bounded by
the  C’s of 5 successive amino acid residues
•6 coplanar atoms of 1 peptide bond: Cα(n)–CO–NH–
Cα(n+1)from  C of one residue to a C of next residue)
•Peptide animation: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/peptide/peptice.html
•Secondary structures stabilized mainly by hydrogen bonds
between backbone amide N–H groups and carbonyl O:’s
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 helix
•
•
•
•
backbone coiled (spiral) conformation -- rod-like structure
Usually right-handed in proteins
R groups radiate outward from helical “cylinder”
Backbone -- regular, repeating rotation, residue by residue:
Each residue has close to the same ( ,) coordinates.
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Berg et al., Fig. 2-29
•
 helix
Animations:
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha/alpha.html
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/helices/helices.html
•
•
Hydrogen bonding pattern for  helix: H bonds almost parallel to helix axis,
from carbonyl O: of residue n to H–N group of residue (n+4).
3.6 residues per 360° turn of  helix.
(N)(+)
•Whole  helix a dipole:
- each peptide bond has
dipole moment
- dipole moments are vectors,
so they sum to make a net
C
dipole for the helix
•N-term end +
•C-term end –
3.6
residues
N
I
H
O
II
This is best seen in the ball and
stick diagram on previous slide (C)(–)
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Ramachandran Plot, (, ) angles for  helix
• For regular, repeating local structures like  helix, each residue has ~ the
same (,) angles. ( conformation has a different set of (,) values.)
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Berg et al. Fig. 2-31
What terminates an -helix?
Statistically, a very high percentage (~60%) of helices are terminated by a single amino acid,
Proline:
The formation of the cyclic structure between
the 3 C R-group and the -N results
eliminates free rotation around the -bond.
Proline is sometimes called the helix
“breaker”.
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Proteins with a lot of the polypeptide chain in
-helical conformation
• Jmol structures of some -helical proteins
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/alpha_domain/alpha_domain.html
Examples: Ferritin (an iron storage protein)
Berg et al., Fig. 2-33
Myoglobin (O2-binding protein
especially rich in muscle cells)
<–– space-filling
atoms (all non-H
atoms shown)
Ribbon rendition ––>
shows only the
polypeptide backbone
tracing in space
Nelson & Cox, Lehninger Principles of
Biochemistry, 4th ed., Fig. 4-16
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Coiled coils of  helices in some proteins
• 2 right-handed -helices coiled around each other in left-handed
direction
• Supercoiled structure has great tensile strength (like a rope with twisted
strands).
• Examples:
- -keratin (a fibrous protein -- elongated 3-dimensional structure, waterinsoluble) -- mammalian hair, quills, claws, horns
– Some globular proteins (compact 3-D structure) -- examples:
• Some transcriptional regulator proteins (“leucine zipper” motif)
• Myosin (muscle)
Berg et al., Fig. 2-43
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 conformation
• Backbone nearly fully extended (not coiled)
• All residues in -sheet have ~ the same (f,y) angles
• Distance between adjacent AA residues ~3.5 Å (further
apart, more stretched out, than in -helix)
• Side chains (R groups) point in alternate/opposite directions
for adjacent residues in chain
• N-H group and C=O group of peptide bond point in opposite
directions, away from average direction of extended
backbone of chain
Berg et al.,
Fig. 2-35
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 conformation
• Backbone amide N-H and C=O groups again almost fully
hydrogen-bonded, but hydrogen bonds can be between
different sections of the backbone OR between sections of
backbone on different polypeptide chains.
• No predictable relationship in the amino acid sequence for
what sections are hydrogen bonded to each other
• Hydrogen bonds more or less at right angles to direction of
backbone of chain
Antiparallel 
conformation
(strands run in
opposite
directions)
Berg et al.,
Fig. 2-36
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 conformation
Parallel 
conformation
(strands run in
same direction)
Berg et al., Fig. 2-37
Mixed 
conformation
(mixture of
parallel and
antiparallel
strands)
Berg et al., Fig. 2-38
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Ramachandran Plot: (, ) angles for  conformation
• For regular, repeating local structures like  helix or for  conformation,
each residue has ~ the same (,) angles. ( conformation has its own
set of (,) values, different from  helix.)
Left-handed
alpha helix
Right-handed
alpha helix
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Berg et al. Fig. 2-34
 pleated sheets
• 4-stranded antiparallel β pleated sheet
• planes of peptide bonds ("pleats") indicated
• R groups (yellow) alternately extending above and below sheet.
Garrett & Grisham,
Biochemistry, 3rd ed.,
Fig. 6-10
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 pleated sheets
• 3-stranded antiparallel β pleated sheet
• planes of peptide bonds ("pleats") indicated
• R groups (purple) alternately extending above and below sheet.
Nelson & Cox, Lehninger
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Principles of Biochemistry,
3rd ed., Fig. 4-7a
 pleated sheets
• 3-stranded parallel β pleated sheet
• planes of peptide bonds ("pleats") indicated
• R groups (purple) alternately extending above and below sheet.
Nelson & Cox, Lehninger
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Principles of Biochemistry,
3rd ed., Fig. 4-7b
Examples of  conformation in proteins
• Jmol structures of  barrel and  clam proteins
http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/beta_domain/beta_domain.html
• twisted  sheet (A: ball & stick; B: ribbon model; C: ribbon model from
"side" to show "twist") (Berg et al., Fig. 2-39)
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Berg et al., Fig. 2-39
Examples of  conformation in proteins
• Fatty acid binding protein
(mostly  conformation;  sheet
in a “clam” motif
• Green fluorescent protein
( barrel structure; used as a
“reporter” in molecular genetics
experiments)
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Berg et al., Fig. 2-40
 turns (reverse turns,  hairpins,  bends)
• Abrupt change in direction of polypeptide backbone, at surface of
protein
• Stabilized by hydrogen bond across “stem” of hairpin
• Sharp turn in space --> steric problems with larger amino acid side
chains
– often involve Gly, Asn, Ser (small hydrophilic residues) or
– Pro (has “built-in” elbow/bend in backbone to help start turn)
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Berg et al., Fig. 2-41
“Loops” (not really “secondary structure”)
•
•
•
•
No regular, recognizable or periodic structures
Longer “excursions” of backbone than simple reverse turns
Usually at surface of protein
Often mediate interactions with other molecules
• Example: loops in antibodies
• Figure shows structure of one
domain of an antibody polypeptide
(red loops involved in binding
antigen; flexible structures in
loops interact with antigen).
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Berg et al., Fig. 2-42
Up next:
• Tertiary structure: 3-dimensional conformation of whole
polypeptide in its folded state
• Quaternary structure: 3-dimensional relationship of the
different polypeptide chains (subunits) in a multimeric
protein; the way the subunits fit together and their
symmetry relationships
– Only in proteins with more than one polypeptide chain
– Proteins with only one chain have no quaternary
structure.
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Learning Objectives
• Define secondary structure.
• List examples of categories of secondary structure that
occur in proteins.
• Describe the -helix, including what groups serve as
hydrogen bond donors and acceptors, chirality of most helices in proteins (right- or left-handedness), number of
residues per turn, orientation of R groups relative to axis of
the helix, the helix dipole (which end is +, which is –), and
packing density of atoms.
• Describe -conformation, including which groups serve as
hydrogen bond donors and acceptors, and orientation of R
groups in a  pleated sheet.
• Explain parallel and antiparallel  conformation.
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Learning Objectives, continued
• Identify the most important noncovalent interactions
stabilizing the -helix and -conformations.
• Explain what a -turn is, where -turns are often found in
proteins, and what types of amino acid residues are often
found in -turns.
• Be able to identify -helices and -strands (or sheets
consisting of 2 or more -strands) on a ribbon depiction of
a protein structure.
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