Antibody Structure
Introduction
Antibodies are immune system-related proteins
called immunoglobulins. Each antibody consists
of four polypeptides– two heavy chains and two
light chains joined to form a "Y" shaped
molecule.
The amino acid sequence in the tips of the "Y"
varies greatly among different antibodies. This
variable region, composed of 110-130 amino
acids, give the antibody its specificity for binding
antigen. The variable region includes the ends of
the light and heavy chains. Treating the antibody
with a protease can cleave this region, producing
Fab or fragment antigen binding that include the
variable ends of an antibody. Material used for
the studies shown below originated from Fab.
The constant region determines the mechanism
used to destroy antigen. Antibodies are divided
into five major classes, IgM, IgG, Iga, IgD, and
IgE, based on their constant region structure and
immune function.
The variable region is further subdivided into
hypervariable (HV) and framework (FR) regions.
Hypervariable regions have a high ratio of
different amino acids in a given position, relative
to the most common amino acid in that position.
Within light and heavy chains, three hypervariable
regions exist – HV 1, 2 and 3. Four FR regions
which have more stable amino acids sequences
separate the HV regions.
The HV regions directly contact a portion of the
antigen's surface. For this reason, HV regions are
also sometimes referred to as complementarity
determining regions, or CDRs. The FR regions
form a beta-sheet structure which serves as a
scaffold to hold the HV regions in position to
contact antigen.
Antibody/Antigen Interaction
Click on images to see enlarged view
This image
represents the
structure of an
antibody's variable
region (Fab)
complexed with an
antigen, in this
case hen egg white
The HV regions of
a Fab, representing
both light and
heavy chains, are
highlighted in
purple. The antigen
is green. The part
of the antigen in
In this view, the
HV regions of the
Fab have been
deleted. The FR
regions of the
antibody do not
contact the antigen.
This ribbon
structure shows the
antibody's HV
(purple) and FR
(yellow) regions of
the Fab, and their
interaction with an
epitope of the
lysozyme. The
other images in this
section are derived
from this structure.
direct contact with
the antibody is
called the antigenic
determinant, or
epitope.
antigen.
Animation: FR and
HV regions of
antibody
Animation:
Antigen interacts
with HV region
Antibody/Antigen Interaction – A Closer Look
An antigenic determinant, a site on the antigen that the immune
system responds to by making antibody, can frequently be one
unique structure on the antigen. In hen egg white lysozyme, a
glutamine at position 121 (Gln 121) protrudes away from the
antigen surface. In this view, Gln 121 is circled. The antibody is not
shown. The following images show how this feature is important for
the formation of a high affinity antibody-antigen interactions.
The antibody's HV region forms an opening to surround the
antigen's protruding Gln 121 (green). Hydrogen bonds (yellow)
stabilize the antibody-antigen interaction. In addition to hydrogen
bonds, other weak interactions such as van der Waals forces,
hydrophobic interactions and electrostatic forces improve the
binding specificity between antibody and antigen. These
interactions occur over large and sometimes discontinuous regions
of the molecules, improving binding affinity. The animation shows
amino acids of the antibody that interact with Gln 121.
Animation: Gln 121 of lysozyme surrounded by amino acid residues
of antibody
Close-up of a hydrogen bond – The Tyr 101 of the antibody forms a
hydrogen bond with the Gln 121 of the antigen.
Water molecules (light blue) fill in spaces between the antigen and
the antibody. The water molecules contribute significantly to the
binding energy by creating additional hydrogen bonds.
Molecular structures represented in this tutorial were obtained by X-ray crystallography.
The coordinates for these structures are registered at the Protein Data Bank (1FYA and
1FYB).