Secondary Protein Structure

What to Know
You will only be tested on what is discussed in class
Pay particular attention to topics that are stressed or mentioned several times
Most important are the general principles, not details that require memorization

Know the classes of secondary structure

Types of helices and how amide plane influences secondary structure of helices
Types of pleated sheets
main differences between the structure of an -helix and a -pleated sheet
What is the main cause of sterically forbidden regions of and ?
What type bonds stabilize secondary structures?
How do you use the helical wheel?
What influences stability of different helices and the different types of -
pleated sheets?
 PROTEIN SECONDARY STRUCTURE

Relatively short-range in globular proteins.

Usually long-range in fibrous proteins.
All bond angles are equal and all
bond angles are equal providing a
repetitive (periodic) structure.
Stability attained through H-bonds.
 Main Classes of Secondary Structure

All these are local structures that are stabilized

by hydrogen bonds
Alpha helix
Beta sheet (composed of "beta strands")
Tight turns (beta turns or beta bends)
 What Are the Elements of Secondary Structure in
Proteins, and How Are They Formed?

The amide or peptide bond planes are

joined by the tetrahedral bonds of the -
carbon.

The rotation parameters are and .

The conformations shown corresponds
to = 180 and = 180.

One can specify a polypeptides

backbone conformation by the torsion
angles (rotation angles) about the Ca-N
bond (f) and Ca-C bond (y) of each of
its amino acid residues
 Consequences of the Amide Plane

Two degrees of freedom per residue for the peptide

chain

Angle about the C-N bond is denoted (phi)

Angle about the C-C bond is denoted (psi)

The entire path of the peptide backbone is known if all

and angles are specified

Some values of and are more likely than others.

Many of the possible conformations about an -carbon between
two peptide planes are forbidden because of steric crowding.
Several noteworthy examples are shown here.
 Protein Structure
Sterically forbidden conformations are those in
which any nonbonding interatomic distance is
less than its corresponding van der Waals
distance
G. N. Ramachandran was the first to
demonstrate the convenience of plotting phi,psi
combinations from known protein structures
The sterically-favorable combinations are the
basis for preferred secondary structures
Steric Constraints on &

Ramachandran diagram showing the

sterically reasonable values of the angles
& .

Shaded regions indicate particularly

favorable values of these angles.

Dots in purple indicate actual angles

measured for 1000 residues (excluding
glycine, for which a wider range of angles
is permitted) in eight proteins.
 Hydrogen Bonds in Proteins

A hydrogen bond between a a

backbone C=O and a backbone N-H
in an acetylcholine binding protein
of a snail, Lymnaea stagnalis.

Schematic drawing of a hydrogen

bond between a backbone C=O
and a backbone N-H.
 Protein Structure
Helical Structures
if a polypeptide chain is twisted by the same
amount about each of its Ca atoms, it assumes a
helical conformation
helix characterization
n=number of peptide units per helical turn
pitch=distance helix rises along axis/turn
helixes have chirality
 Protein Structure
Helical Structures
If a particular helix is to be more than transient,
it must be stabilized (H-bonds)
Only one helical polypeptide conformation has
simultaneously allowed conformation angles and
a favorable hydrogen binding pattern: a=helix, a
particularly rigid arrangement of the polypeptide
chain. Designation: 3.613 p=5.4
 The -Helix

Four different representations of the -helix

First proposed by Linus Pauling and Robert Corey in 1951
A ubiquitous component of proteins, stabilized by H bonds
 Protein Structure

Other Helical Structures

310 helix: p=6.0
frequently occurs as a single turn transition
between the end of an a-helix and the next
portion of the polypeptide chain

p helix (4.416 helix): p=5.2

comparatively wide and flat conformation
results in axial hole too small to admit H2O
yet too wide to allow van der Waals
associations across the helix axis
 Exposed N-H and C=O groups at the ends of an
-Helix can be capped.

Four N-H groups at the N-terminal end of an -

helix and four C=O groups at the C-terminal end
lack partners for H-bond formation.
An amphiphilic helix
in flavodoxin:

A nonpolar helix in
citrate synthase:

A polar helix
in calmodulin:
 The Beta-Pleated Sheet

Formed through by side-by-side alignment of

polypeptide strands
Strands may be parallel or antiparallel
Stability arises via H-bond interactions
Distance: 3.5Ao for antiparallel strands
3.3Ao for parallel strands
Each strand of a beta sheet may be pictured as a
helix with two residues per turn
 An antiparallel -pleated sheet. R groups project alternately above and below the plane of the
sheet. Sheet structure is derived from the tetrahedral placement of substituents on the
carbon atoms. This is the more stable form of a -sheet.
Arrangement of hydrogen bonds
in (a) parallel and (b) antiparallel
-pleated sheets.
Parallel sheets: Large;
hydrophobic on both sides of
sheet; interior of globular proteins.

Antiparallel sheets: 2-3 strands;

amphipathic allowing good
boundaries with aqueous
surroundings.
 Protein Structure
Beta structure
-pleated sheets in globular proteins
typically exhibit a right-handed twist when
viewed along their polypeptide strand
twists serve important role since sheets often
form central core of proteins
in globular proteins, sheets are common
parallel sheets of less than 5 strands are rare,
suggesting they are less stable than antiparallel
sheets (H-bonds are distorted for parallel sheets)
 Protein Structure

Beta structures
mixed parallel-antiparallel sheets are
common but occur less frequently than
expected from random mixing of
strands
 The Beta Turn

allows the peptide chain to reverse direction

carbonyl C of one residue is H-bonded to the
amide proton of a residue three residues away
proline and glycine are prevalent in beta turns
The structures of two kinds of -turns (also called tight turns or -bends).
Proline and glycine are frequently situated in positions 2 and 3, respectively.
 Protein Structure

Beta structures
links between 2 antiparallel
sheets=hairpin turn
links between 2 parallel sheets=cross-
over connection
 Fibrous Proteins

Much or most of the polypeptide chain is

organized approximately parallel to a single axis
Fibrous proteins are often mechanically strong
Fibrous proteins are usually insoluble
Usually play a structural role in nature
 Alpha Keratin

Found in hair, fingernails, claws, horns and

beaks
Sequence consists of 311-314 residue alpha
helical rod segments capped with non-helical
N- and C-termini
Primary structure of helical rods consists of 7-
residue repeats: (a-b-c-d-e-f-g)n where a and
d are nonpolar. Promotes association of
helices!
(a) Both type I and type II a-keratin molecules have sequences consisting of long,
central rod domains with terminal cap domains. Asterisks denote domains of
variable length.
(b) (b) The rod domains form coiled coils consisting of intertwined right-handed a-
helices. These coiled coils then wind around each other in a left-handed twist.
Keratin filaments = twisted protofibrils (each a bundle of four coiled coils)
 Beta Keratin
Found in silk fibers
Alternating sequence:
Gly-Ala/Ser-Gly-Ala/Ser....
Since residues of a beta sheet extend alternately above
and below the plane of the sheet, this places all
glycines on one side and all alanines and serines on
other side!
This allows Glys on one sheet to mesh with Glys on an
adjacent sheet (same for Ala/Sers)
Silk fibroin consists of a unique stacked array of b-sheets. The primary
structure of fibroin molecules consists of long stretches of alternating glycine
and alanine or serine residues.
When the sheets stack, the more bulky alanine and serine residues on one
side of a sheet interdigitate with similar residues on an adjoining sheet.
Glycine hydrogens on the alternating faces interdigitate in a similar manner,
but with a smaller intersheet spacing.