G09SecL04Tpc2: Difference between revisions

(17 intermediate revisions by 2 users not shown)

Line 1:

'''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 [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=~~art8~~>PMID 16040645</ref~~> <Structure load='1FJ1' size='400' align='right' caption='OspA Dimer with LA-2 Antibody DImer'/~~>

'''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>

Line 5:

Line 6:

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) ==

=== Structural Breakdown ===

<scene name='G09SecL04Tpc2/Newfirst/1'>Reset Model</scene>

Line 17:

Line 18:

'''Scene List:'''

*<scene name='G09SecL04Tpc2/Newfirst/1'>Reset Model</scene>

*<scene name='G09SecL04Tpc2/3loops/1'>Loop 1</scene>

*<scene name='G09SecL04Tpc2/3loops/2'>Loop 2</scene>

Line 28:

Line 30:

=== LA-2 Recognition ===

<scene name='G09SecL04Tpc2/Ospala2/1'>Reset Model</scene>

Line 48:

Line 50:

====Inactivation of effector mechanisms====

Besides extensive down-regulation upon infection of the host, ''b.burgdorferi'' can make it even harder for the body to carry out a successful immune response. The borrelia can express complement-binding surface proteins, which prevents complement-mediated killing once inside the host regulated by the host’s immune system<ref name=art4>PMID:18097481</ref>. Although prior vaccination before infection is ideal, it is also important to develop and continue antibiotic research that can be administered after infection. In addition to eluding the immune system through these newly expressed surface proteins, borrelia also possesses the potential to activate anti-inflammatory [http://en.wikipedia.org/wiki/Cytokine cytokines] such as Interleukin 10<ref name=art4>PMID:18097481</ref>. Ultimately, this suggests that borrelia can decrease inflammation by inducing IL-10 and preventing the host immune system from marking regions of antigenic activity. This can also delay or possibly halt the attack of leukocytes. Lastly, recent studies have shown that ''b.burgdorferi'' releases antigens that are soluble<ref name=art4>PMID:18097481</ref>. These antigens mingle with the antibodies that are specific for b.burgdorferi and prevent the antibodies from carrying out their role in defense. Not only does borrelia demonstrate abilities of suppressing the immune response, but also dramatically weakens the reliable effector mechanisms of the host immune system.

Besides extensive down-regulation upon infection of the host, ''b.burgdorferi'' can make it even harder for the body to carry out a successful immune response. The borrelia can express complement-binding surface proteins, which prevents complement-mediated killing once inside the host regulated by the host’s immune system.<ref name=art4>PMID:18097481</ref> Although prior vaccination before infection is ideal, it is also important to develop and continue antibiotic research that can be administered after infection. In addition to eluding the immune system through these newly expressed surface proteins, borrelia also possesses the potential to activate anti-inflammatory [http://en.wikipedia.org/wiki/Cytokine cytokines] such as Interleukin 10.<ref name=art4>PMID:18097481</ref> Ultimately, this suggests that borrelia can decrease inflammation by inducing IL-10 and preventing the host immune system from marking regions of antigenic activity. This can also delay or possibly halt the attack of leukocytes. Lastly, recent studies have shown that ''b.burgdorferi'' releases antigens that are soluble.<ref name=art4>PMID:18097481</ref> These antigens mingle with the antibodies that are specific for b.burgdorferi and prevent the antibodies from carrying out their role in defense. Not only does borrelia demonstrate abilities of suppressing the immune response, but also dramatically weakens the reliable effector mechanisms of the host immune system.

====Hiding in the Extracellular Matrix====

G09SecL04Tpc2: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''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 [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=art8>PMID 16040645</ref> <Structure load='1FJ1' size='400' align='right' caption='OspA Dimer with LA-2 Antibody DImer'/>
+<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>
@@ Line 5: / Line 6: @@
 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) ==
 === 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>
@@ Line 17: / Line 18: @@
 '''Scene List:'''
+*<scene name='G09SecL04Tpc2/Newfirst/1'>Reset Model</scene>
 *<scene name='G09SecL04Tpc2/3loops/1'>Loop 1</scene>
 *<scene name='G09SecL04Tpc2/3loops/2'>Loop 2</scene>
@@ Line 28: / Line 30: @@
 === 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>
@@ Line 48: / Line 50: @@
 ====Inactivation of effector mechanisms====
-Besides extensive down-regulation upon infection of the host, ''b.burgdorferi'' can make it even harder for the body to carry out a successful immune response. The borrelia can express complement-binding surface proteins, which prevents complement-mediated killing once inside the host regulated by the host’s immune system<ref name=art4>PMID:18097481</ref>. Although prior vaccination before infection is ideal, it is also important to develop and continue antibiotic research that can be administered after infection. In addition to eluding the immune system through these newly expressed surface proteins, borrelia also possesses the potential to activate anti-inflammatory [http://en.wikipedia.org/wiki/Cytokine cytokines] such as Interleukin 10<ref name=art4>PMID:18097481</ref>. Ultimately, this suggests that borrelia can decrease inflammation by inducing IL-10 and preventing the host immune system from marking regions of antigenic activity. This can also delay or possibly halt the attack of leukocytes. Lastly, recent studies have shown that ''b.burgdorferi'' releases antigens that are soluble<ref name=art4>PMID:18097481</ref>. These antigens mingle with the antibodies that are specific for b.burgdorferi and prevent the antibodies from carrying out their role in defense. Not only does borrelia demonstrate abilities of suppressing the immune response, but also dramatically weakens the reliable effector mechanisms of the host immune system.
+Besides extensive down-regulation upon infection of the host, ''b.burgdorferi'' can make it even harder for the body to carry out a successful immune response. The borrelia can express complement-binding surface proteins, which prevents complement-mediated killing once inside the host regulated by the host’s immune system.<ref name=art4>PMID:18097481</ref>  Although prior vaccination before infection is ideal, it is also important to develop and continue antibiotic research that can be administered after infection. In addition to eluding the immune system through these newly expressed surface proteins, borrelia also possesses the potential to activate anti-inflammatory [http://en.wikipedia.org/wiki/Cytokine cytokines] such as Interleukin 10.<ref name=art4>PMID:18097481</ref> Ultimately, this suggests that borrelia can decrease inflammation by inducing IL-10 and preventing the host immune system from marking regions of antigenic activity. This can also delay or possibly halt the attack of leukocytes. Lastly, recent studies have shown that ''b.burgdorferi'' releases antigens that are soluble.<ref name=art4>PMID:18097481</ref>  These antigens mingle with the antibodies that are specific for b.burgdorferi and prevent the antibodies from carrying out their role in defense. Not only does borrelia demonstrate abilities of suppressing the immune response, but also dramatically weakens the reliable effector mechanisms of the host immune system.
 ====Hiding in the Extracellular Matrix====