Protein: 3DSF
Anti-Osteopontin
Antibody 23C3 in Complex with W43A Mutated Epitope Peptide
This
protein is an antibody associated with an extracellular linking protein called
osteopontin that has been linked to the auto-immune disease Rheumatoid
Arthritis. This antibody-eptitope
peptide complex is the foundation of hopeful treatment for patients suffering
with this auto-immune condition that consists of inflammation and damage of the
body’s synovial joints by the immune system.
Patients
with Rheumatoid Arthritis have greater than normal amounts of osteopontin
present in their synovial tissue. It has
been shown experimentally that osteopontin plays a role in the pathogenesis of RA:
one that recruits inflammatory cells through chemotactic action, bringing more
immune cells to the synovium, increasing inflammation and ultimately causing
more damage to the joints. The use of
this antibody/epitope peptide protein complex may offer therapeutic relief for
RA patients in the development of drug treatments based on the binding site to osteopontin, to block its chemotactic activities
and reduce T-cell responses, which in turn will decrease the amount of
inflammatory cells and damage to the joints.
Inclusion of the specific epitope offers an additional range of
possibilities for the development for new drugs to treat RA disease.
Primary Structure:
A
total of 441 residues are found in this protein complex.
Secondary Structure:
This
antibody/epitope peptide complex consists of mainly beta sheets with a small
percentage of helices and a short peptide from the osteopontin protein.
Tertiary Structure:
The
forces and interactions involved in 3DSF determine its structure as a globular protein.
Quarternary Structure:
3
chains make this protein complex a trimer. Typically antibodies exist as tetramers,
containing 4 very flexible chains: two long, heavy chains and two short, light
chains. However, the flexible nature of
these globular proteins makes it extremely difficult to study them intact. The specific structure for 3DSF contains a
heavy chain (H), a light chain (L) and a peptide from osteopontin:
Chain
H: Fab fragment of anti-osteopontin
antibody 23C3, Heavy chain
5% helical (4
helices; 12 residues)
48% beta sheet
(21 strands; 104 residues)
Chain
L: Fab fragment of anti-osteopontin
antibody 23C3, light chain
3% helical (2
helices; 7 residues)
49% beta sheet
(21 strands; 106 residues)
Chain
P: Peptide from osteopontin (12
residues)
Much
of the immune response and attack of the synovium in Rheumatoid Arthritis is
still not completely understood and medications that have historically been
used to treat this autoimmune condition can be harsh and often have many undesirable
side effects. Recently there has been a
surge of research into the mechanisms involved in the pathogenesis of RA and other
autoimmune diseases, offering a promise of more effective biological
treatment. It is clear that osteopontin
plays a role in RA and several other autoimmune conditions. The development of this protein complex may
offer new potentially more effective and less harsh therapeutic possibilities to those who suffer with RA.
For additonal information:
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