User:Marvin O'Neal/OspC
From Proteopedia
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== Ecology of Lyme Disease == | == Ecology of Lyme Disease == | ||
| + | The reported cases of Lyme disease are increasing annually in highly focused geographic locations such as northeastern and north central regions of the United States. Thus, the abundance of ticks with ''B. burgdorferi'' in natural ecosystems is critical for the prevalence of Lyme disease. The larval ticks become infected while feeding on the blood of natural reservoir hosts such as mice, squirrels, shrews and other small vertebrates. Persisting to successive life stages, the infected nymphal ticks can transmit ''B. burgdorferi'' to incidental vertebrates, including humans. | ||
== Ecological factors responsible for Human Lyme disease risk == | == Ecological factors responsible for Human Lyme disease risk == | ||
Revision as of 19:01, 29 April 2012
Hello!
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| 1ggq, resolution 2.51Å () | |||||||||
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| Ligands: | |||||||||
| Related: | 1f1m, 1osp, 1fj1 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Introduction
Lyme disease is a typical epidemic in northeastern and north central regions of the United States. It is also the most prevalent tick-borne disease which is caused by Borrelia burgdoferi,a spirochete that is identified in Ixodes scapulars. Humans infected with Lyme disease begin with unusal skin lesions (erythema chronicum migrans), which later develop into more severe neurological and cardiac symptoms. If it is not completely treated, the causative agent of Lyme disease persists in human by interacting the surface-exposed B. burgdoferi proteins with the molecules of the host. Among 100 different lipoproteins present in its outer surface, the outer surface protein C (OspC) is one of its major host-induced antigens, but is inactive due to the immune response of mammalian host during its early age. The expression of OspC is dependent on temperature and it is induced when the tick migrates from guts to salivary gland during feeding period. OspC is highly polymorphic that based on alignment sequence its genetic diversity at the OspC locus that can be categorized into 19 outer surface protein major groups (oMGs) ranged from type A to S. However, only four invasive allelic groups: A, B, I(1f1m), and K, are responsible for causing human Lyme disease.
Ecology of Lyme Disease
The reported cases of Lyme disease are increasing annually in highly focused geographic locations such as northeastern and north central regions of the United States. Thus, the abundance of ticks with B. burgdorferi in natural ecosystems is critical for the prevalence of Lyme disease. The larval ticks become infected while feeding on the blood of natural reservoir hosts such as mice, squirrels, shrews and other small vertebrates. Persisting to successive life stages, the infected nymphal ticks can transmit B. burgdorferi to incidental vertebrates, including humans.
Ecological factors responsible for Human Lyme disease risk
Dilution Effect Model
Structure of outer surface protein C (OspC)
The model presented is B31 strain (residues 38-201), which is also known as oMG A. This is one of four invasive oMGs that are responsible for systematic Lyme disease. In crystal structure, OspC exists as a with the coordination of divalent ion, which is modeled as a magnesium ion. Each subunit is predominantly helical, consisting of five parallel , two short antiparallel and six . Since the loop regions are the most antigenic sites on the protein, pink and red colors were applied to protein in order to differentiate the polymorphism among these major antigenic sites [1]. The on the protein, residue 146 to 150 and residue 77 to 93, are colored in red. Two short β sheets are included in this region. On the other hand, two , residue 115 to 119 and residue 161 to 169, are colored in pink. Among these polymorphic antigenic regions, the amino acid sequence of the invasive oMGs appears to be similar to each other while the sequences from non-invasive ones are diverged and are substituted with amino acids different from the invasive strains.
82nd amino acid residue
The , Histidine, with CPK colors is a more specific region to show polymorphic antigenic site on the protein. This position is unique that all the non-invasive oMGs contain amino acid other than Histidine, Lysine or Glutamine. The oMG strains have higher possibilities to be pathogenic when the 82nd position is occupied by Histidine, Lysine, or Glutamine. The stronger the electrostatic on loop regions, the higher chance for OspC to binds with positively charged human ligands. [2] Therefore, an alternation of amino acid at the 82nd position not only shows OspC polymorphism, but also points out the probability for turning invasive strains to non-invasive strains.
References
- ↑ Earnhart C, LeBlanc D, Alix K, Desrosiers D, Radolf J, and Marconi R. 2010. Identification of residues within ligand-binding domain 1 (LBD1) of the Borrelia burgdorferi OspC protein required for function in the mammalian environment. Molecular Microbiology 76(2): 393-408. DOI: 10.1111/j.1365-2958.2010.07103.x
- ↑ Kumaran D, Eswaramoorthy S, Luft B, Koide S, Dunn J, Lawson C, and Swaminathan S. 2001. Crystal Structure of Outer Surface Protein C (OspC) from the Lyme Disease Spirochete, Borrelia burgdorferi. The EMBO Journal 20(5): 971-978. DOI: 10.1093/emboj/20.5.971
