G09SecL04Tpc2

2012-08-16T10:03:33Z

Amar Patole:

[[Image:Ospapic2.gif|thumb|right|Scanning electron micrograph of the spirochete ''Borrelia burgdorferi'', causative agent of Lyme disease.]]

'''Outer Surface Protein A (OspA)''' is a major [http://en.wikipedia.org/wiki/Lipoprotein lipoprotein] on the ''borrelia burgdorferi'' [http://en.wikipedia.org/wiki/Spirochete spirochete] which is a causative agent of Lyme Disease. The three loops in the C-terminus define the OspA antigen-antibody complex. The interaction between the loops and the LA-2 (antibody) forms the basis for OspA vaccination. Along with other surface proteins, OspA has many important functions that are associated with [http://en.wikipedia.org/wiki/Lyme_Disease Lyme Disease] such as late stage neurological disorders including acute Lyme [http://en.wikipedia.org/wiki/Neuroborreliosis Neuroborreliosis].

== Introduction to Lyme Disease ==
[[Image:LymeDisease.gif|thumb|left|Bull-Eye Rash. Courtesy of CDC.]]
Lyme disease is the most common tick-borne disease in North American hemisphere. Responsible for transmission is a tick vector from the genus of [http://en.wikipedia.org/wiki/Ixodidae Ixodidae]. There are different bacterial strains of borrelia including ''B.afzellii'' and ''B.garinii'' being very prevalent throughout the European continent; other known strains such as ''B.dutonii'' and ''B. recurrentis'' have been discovered within the past few decades. The most common strain in the United States is [http://en.wikipedia.org/wiki/Borrelia_burgdorferi ''borrelia burgdorgeri''] sensu stricto, and this treponema-like spirochete was discovered to be the causative agent of Lyme Disease discovered by Dr. Willy Burgdorferi in 1982 along with several other colleagues. <ref name=art1>PMID:7043737</ref>

Besides OspA, there are other outer surface proteins, including OspB, OspC, and Vls, which are very important for the transmission of Lyme Disease from the tick to the host, as well as establishing the infection via bloodstream disseminating throughout the host body. Early symptoms of Lyme Disease include skin lesions and rashes that have a characteristic bulls-eye appearance known as [http://en.wikipedia.org/wiki/Erythema_chronicum_migrans erythema chronicum migrans (ECM)]. It is important to note that ECM can be used for early diagnosis of Lyme Disease prior to awaiting more accurate laboratory tests. <ref name=art2>PMID:17029130</ref>

Upon infection, OspA is immediately downregulated or can even be turned off. Because of this, vaccinations for OspA are virtually ineffective once spirochetes have entered the host. Downregulation also makes OspA harder to detect; OspA is usually upregulated in the late stages of the disease and leads to more serious inflammatory disorders in the central nervous system.

== Outer Surface Protein A (OspA) ==
=== Structural Breakdown ===
<Structure load='1fj1' size='350' frame='true' align='right' caption='Outer Surface Protein A' scene='G09SecL04Tpc2/Startospa/3' />
<scene name='G09SecL04Tpc2/Startospa/3'>Reset Model</scene>

Outer Surface Protein A has approximately 270 amino acid residues. <ref name=art3>PMID:11183781</ref>In terms of secondary structure, OspA is made up of 21 anti-parallel single layer beta strands and one alpha helix. <ref name=art3>PMID:11183781</ref>OspA has three major components to its structure: an <scene name='G09SecL04Tpc2/3sites/3'>n-terminal sandwich</scene>, <scene name='G09SecL04Tpc2/3sites/2'>a central sheet</scene>, and a <scene name='G09SecL04Tpc2/3sites/4'>c-terminal barrel domain</scene>. The n-terminal is often termed as a sandwich due to its jumbled formation of amino acid residues. Most of the beta strands lie on the central sheet. Lastly, the c-terminal is called barrel domains because the three primary loops connect to both sides of the central beta sheet forming a barrel or a hole in the middle. This can be seen by rotating the molecule.

The c-terminal is heavily involved in the antigen:antibody complex unlike the n-terminal. The c-terminal houses a protruding ridge of three loops: <scene name='G09SecL04Tpc2/3loops/1'>loop 1</scene> contains residues 203-220; <scene name='G09SecL04Tpc2/3loops/2'>loop 2</scene> contains residues 224-233; <scene name='G09SecL04Tpc2/3loops/3'>loop 3</scene> contains residues 246-257. These loops define the LA-2 (antibody) [http://en.wikipedia.org/wiki/Epitope epitope]. More specifically, the loops indicate where the antibody binds to the antigen. This protruding ridge coupled with OspA’s elongated fold gives the surface protein a high degree of mobility and surface exposure. Loops 2 and 3 tend to be more conserved.

<scene name='G09SecL04Tpc2/3loops/4'>View All 3 Loops</scene>

=== LA-2 Recognition ===

=== The Elusiveness of OspA ===

<ref name=art4>PMID:18097481</ref>

==Additional Resources==
*[http://www.wadsworth.org/databank/borreli.htm Wadsworth Center: NYS Department of Health]
*[http://www.rcsb.org/pdb/home/home.do RCSB Protein Data Bank]
*[http://www.cdc.gov/lyme/ CDC: Lyme Disease]

==References==

<references />

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