G09SecL04Tpc2: Difference between revisions
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'''Outer Surface Protein A (OspA)''' is a major | <Structure load='1FJ1' size='400' frame='true' align='right' caption='OspA Dimer (magenta and cyan) with LA-2 Antibody DImer; light chain(grey and pink), heavy chain (green and yellow) (PDB code [[1fj1]]) '/> | ||
'''Outer Surface Protein A (OspA)''' is a major lipoprotein on the ''borrelia burgdorferi'' [http://en.wikipedia.org/wiki/Spirochete spirochete], which is a causative agent of [http://en.wikipedia.org/wiki/Lyme_Disease Lyme Disease]. The three loops in the C-terminus define the [http://en.wikipedia.org/wiki/Protein_dimer dimerized] antigen-antibody complex. Shown to the right is the <scene name='G09SecL04Tpc2/Osp_a_dimer_with_la-2_antibody/1'> OspA dimer with LA-2 Antibody complex</scene>. The interaction between the loops and the LA-2 antibody forms the basis for successful OspA vaccination of this infectious disease. Most early symptoms include fever and headaches that are often eliminated through antibiotics. On the other hand, OspA has many important functions that are associated with late stage neurological disorders of the central nervous system including acute Lyme [http://en.wikipedia.org/wiki/Neuroborreliosis Neuroborreliosis], which can be extremely difficult to treat and disabling of the physical body itself.<ref name=art9>PMID 16040645</ref> | |||
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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 [http://en.wikipedia.org/wiki/Borrelia 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> | 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 [http://en.wikipedia.org/wiki/Borrelia 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 (see 3-D Structures below), 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> | Besides OspA, there are other outer surface proteins or [http://en.wikipedia.org/wiki/Lipoprotein lipoproteins], including OspB, OspC, and Vls (see 3-D Structures below), 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> | ||
== Outer Surface Protein A (OspA) == | == Outer Surface Protein A (OspA) == | ||
=== Structural Breakdown === | === Structural Breakdown === | ||
<Structure load='1fj1' size='300' frame='true' align='left' caption='Outer Surface Protein A' scene='G09SecL04Tpc2/Newfirst/1' /> | <Structure load='1fj1' size='300' frame='true' align='left' caption='Outer Surface Protein A [[1fj1]]' scene='G09SecL04Tpc2/Newfirst/1' /> | ||
<scene name='G09SecL04Tpc2/Newfirst/1'>Reset Model</scene> | |||
Outer Surface Protein A has approximately 270 amino acid residues.<ref name=art3>PMID:11183781</ref> In terms of <scene name='G09SecL04Tpc2/Startospa/3'>secondary structure</scene>, OspA is made up of 21 [http://en.wikipedia.org/wiki/Antiparallel_(biochemistry) anti-parallel] single layer beta strands (gold) and one alpha helix (magenta).<ref name=art3>PMID:11183781</ref> OspA has three major components to its structure: an <scene name='G09SecL04Tpc2/Newfirst/2'>n-terminal sandwich</scene>, central sheet, and a c-terminal barrel domain. 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 <scene name='G09SecL04Tpc2/Newfirst/3'> central beta sheet</scene>. Lastly, the <scene name='G09SecL04Tpc2/Newfirst/4'>c-terminal </scene> is nicknamed barrel domains because the three primary loops on the tip of the c-terminus 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. | Outer Surface Protein A has approximately 270 amino acid residues.<ref name=art3>PMID:11183781</ref> In terms of <scene name='G09SecL04Tpc2/Startospa/3'>secondary structure</scene>, OspA is made up of 21 [http://en.wikipedia.org/wiki/Antiparallel_(biochemistry) anti-parallel] single layer beta strands (gold) and one alpha helix (magenta).<ref name=art3>PMID:11183781</ref> OspA has three major components to its structure: an <scene name='G09SecL04Tpc2/Newfirst/2'>n-terminal sandwich</scene>, central sheet, and a c-terminal barrel domain. 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 <scene name='G09SecL04Tpc2/Newfirst/3'> central beta sheet</scene>. Lastly, the <scene name='G09SecL04Tpc2/Newfirst/4'>c-terminal </scene> is nicknamed barrel domains because the three primary loops on the tip of the c-terminus 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. | ||
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=== LA-2 Recognition === | === LA-2 Recognition === | ||
<Structure load='1fj1' size='300' frame='true' align='right' caption='OspA and LA-2 Fab Complex ' scene='G09SecL04Tpc2/Ospala2/1' /> | <Structure load='1fj1' size='300' frame='true' align='right' caption='OspA and LA-2 Fab Complex [[1fj1]] ' scene='G09SecL04Tpc2/Ospala2/1' /> | ||
<scene name='G09SecL04Tpc2/Ospala2/1'>Reset Model</scene> | <scene name='G09SecL04Tpc2/Ospala2/1'>Reset Model</scene> | ||
