Download 1 Protein Structure I I. Proteins are made up of amino acids. Amino

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Protein Structure I
I. Proteins are made up of amino acids. Amino acids share a general structure:
COOH
H 2N
C
R
H
The central carbon (Cα) is asymmetric; that is, the four groups can be arranged
around it in either of two ways (R and S, also called D and L):
HOOC
R
R
COOH
H
NH 2
NH 2
L
S
All amino acids in nature have the L configuration.
Twenty different amino acids are known; they differ in their R groups.
One of these, proline, is technically an imine, not an amine - its R group
forms two bonds with Cα instead of one:
COOH
N
HC
C
C
H
H
CH
An average single-chain protein is 500 amino acids long. The smallest,
insulin, is 51 aa’s - anything smaller is called a polypeptide. Titin, the largest as far
as anyone knows, is 29,926 aa’s in one chain.
II. Peptide bond structure
Amino acids are strung together by peptide bonds between O=C and NH2:
R
O
R
O
R
|
//
|
//
|
H2N----C----C----N----C----C----N----C---- . . .
|
| |
|
|
H
H H
H H
If each bond could rotate through a minimum of three positions, 1030
conformations would be possible for a polypeptide of 21 amino acids. But Linus
Pauling showed that’s nowhere near the case by measuring the dimensions of
2
each bond. He found that:
-- the Cα -- C and the Cα -- N bonds are the expected lengths, BUT
O
//
-- the C -- N bond is shorter than a normal C--N bond, and
--the C=O bond is longer than a general ketone bond.
From this he deduced that the short C-N bond has some double bond
character and that O, C, N and H can be written as resonating between two
structures:
OO
C
C
N
H
N
H+
As a result, these four atoms are planar - and the conformational possibilities
are reduced to whether the groups on either end are cis or trans to each other. It
turns out that all cases are trans due to steric hindrance between R groups in the cis
conformation. All, that is, except for proline, which encounters some steric
hindrance either way and can thus be either cis or trans. Pauling’s discovery has
two additional consequences:
1) Due to the partial negative and positive charges on O and N, the planar
group has an overall dipole moment of 4.5 D (debye units):
O
C
N
C
2) Whole groups rotate around Cα:
N
H
R
O
C
H
C
N
H
R
O
C
H
C
R
N
H
C
H
and thus the conformation of an amino acid is described relative to its
neighbors by specifying the two dihedral angles formed between Cα and the planes
on either side of it.
φ (phi) is the angle between Cα and N
ψ (psi) is the angle between Cα and C=O
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In theory each angle can range from -180˚ to +180˚, but steric hindrance rules
out about 90% of the possible combinations. Out of the sterically allowed values,
only a few distinct sets are found. These values define the main structural motifs of
which all proteins are composed - the right-handed α-helix and the parallel and
antiparallel β-structures.
III. Secondary structures
α-helix - see Figure 7-11, Voet and Voet pg 146
Most cases are right-handed.
R groups all point toward the outside of the helix, and all peptide bonds are on the
inside.
The rise for each turn, or the vertical distance between corresponding parts of
amino acids, is 5.4 angstroms.
The rise per residue is 1.5 Α.
Each turn contains 3.6 amino acids (or 5.4/1.5) - thus, looking down the helix from
a bird’s eye view shows one R group every 100˚ around a circle.
A single chain of helical structure is self-contained.
β-structure - see Figure 7-16, Voet and Voet pg 149
Polypeptide chains are stretched out relative to compressed α-helix;the rise per
residue is 3.5Α vs 1.5Α for a helix.
In a parallel β-sheet, amino acid stretches are parallel to each other; antiparallel βsheets contain amino acid regions running in opposite directions.
Antiparallel sheets kink, forming a pleated sheet with R group pairs alternating in
the direction they face.
IV. Hydrogen bonds favor α-helix and β-structures over other structures
A conformation which brings an electrophilic (electron-poor) atom close to
an electron-rich atom is stabilized by a weak interaction between the two atoms.
----O----H .... N----
or
----N----H....O----
The α-helix conformation allows each CO to hydrogen bond with the NH
four residues up. Although each H-bond is weak, the sum of many H-bonds
throughout the chain provides enough energy to stabilize the helix.
β-sheets are stabilized by hydrogen bonds between CO and NH groups on
adjacent strands..
The particular sequence of R groups causes some chains to form helices and
others to form β-structures.