Download The Structure and Function of Myelin Oligodendrocyte Glycoprotein

The Structure and Function of Myelin
Oligodendrocyte Glycoprotein – MOG
Riverside University High School SMART Team
Katy Keefe, Cristina O’Brien, Hannah Gottinger,
Alyssa Latin-Kasper, Megan McChain
Instructor: Jeff Anderson Mentor: Dr. Bonnie Dittel, Blood Research Institute
Abstract
Autoimmune disorders are the result of the body mounting
an immune response against self-proteins. The T cells target and
destroy these “foreign” proteins. Destruction of the myelin
oligodendrocyte glycoprotein (MOG) located within the myelin
surrounding neurons by T cells can lead to the demyelination of
the nerves, thus producing multiple sclerosis-like symptoms.
Nervous System Function
In the human body our nervous system performs three main
functions of input, integration, and motor output. Input involves the
conduction of signals from sensory receptors to integration centers in the
nervous system. Integration is the processing of information from
environmental stimulation which is read and used to create the appropriate
body responses. Motor output is the actual conduction of signals from
one's brain to the effector cells - the muscle or gland cells that actually
carry out the action.
Looking more closely, neurons are the functional unit of the nervous
system and carry electrical signals from site to site. When your body
senses a stimulus, a message is sent from where the stimulus is felt, to
your brain, then back to react to the stimulus. This response is not an
immediate reaction. For example, compare a giraffe and a human who
both have a weight dropped on their foot. The stimulus will take longer
for the giraffe to react than the human because the signals have farther to
travel. Our neurons function extremely quickly. One reason for this is
that neurons are covered in the myelin sheath. The myelin sheath allows
the signals to jump down the nerves with increased speed.
The protein that we researched, MOG, can be abnormally targeted
for destruction, which may lead to the break down of the myelin sheath
and the development of several diseases.
Supported by the National Institutes of Health - Science Education
Partnership Award (NIH(NIH-SEPA)
Multiple Sclerosis
MOG Model
Multiple Sclerosis (MS) is an inflammatory disease of the Central
Below is pictured the physical model of the MOG Protein.
Nervous System (CNS) that attacks the white matter tissue surrounding the
MOG may function as a dimer. Shown as a monomer.
nerve fibers responsible for transmitting communication signals both within
the CNS and between the CNS and the nerves supplying the rest of the body.
In people affected by MS, areas of damage (lesions) appear in seemingly
random areas of the white matter. At the lesion site a nerve insulating material
called myelin is lost leaving scar tissue called sclerosis. The demyelination is
usually slow but progressive. The site of nerve damage in one person can be
very different from another person with MS. In general, people with MS can
experience partial or complete loss of any function that is controlled by the
brain or spinal cord. The exact cause of MS isn't known but the leading theory
suggests the disease is caused by an autoimmunity dysfunction. Steroids are
the most common way to treat MS, but immunosuppressants are involved in
present experiments.
Normal Myelin
Abnormal Myelin
Myelin Oligodendrocyte Glycoprotein
Myelin oligodendrocyte glycoprotein (MOG) is a relatively small
component of central nervous system myelin; we only see the extracellular
domain in our model. The function of MOG remains somewhat unknown.
MOG is an autoantigen that when targeted for destruction by T cells can lead
to the production of a demyelinating multiple sclerosis-like disease.
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Red – stop codon
Green – start codon
Yellow – beta sheet
Blue – MOG 35 – 55 with side chains*
*MOG 35-55 is the segment important in the process that
causes the body to recognize MOG as a foreign protein.
This is thought to be the leading or most important peptide
strand that is involved in MS. This peptide is what is recognized by
the T cells as a nonself antigen. There are at least 3 different antigens
involved in MS (maybe more).
Conclusion
Recognition of a non-self protein
Demyelination occurs when the oligodendrocytes surrounding a neuron
are destroyed. These cells are targeted after a T cell recognizes a non-self
peptide displayed on the MHC II (major histocompatability complex) of an
antigen-presenting cell.
Throughout this project we struggled as a team to
understand the specific biochemical mechanism that MOG
was involved in. Like many cell processes, the demyelination
of the myelin sheath is very complex and not completely
understood. As is typical of scientific research, we still do
not know the whole story. Over the course of this project we
expanded our knowledge of MOG, auto antigens, research,
and science itself.
RUHS 2003-04 Smart Team