Aralkylamine N-acetyltransferase: Difference between revisions

Revision as of 17:37, 11 February 2025

Overview of antigenic variation in pathogens

Antigenic variation is a mechanism by which an infectious organism alters its surface proteins in order to evade a host immune response. This process is crucial for the survival of many pathogens, allowing them to persist in the host and cause chronic infections. Antigenic variation is a common strategy among viruses, bacteria, and protozoa.

Mechanisms

Antigenic variation can occur through several mechanisms, including:

Gene conversion

Gene conversion involves the replacement of one gene segment with another, leading to the expression of a different antigenic variant. This mechanism is well-studied in the African trypanosome, which uses gene conversion to switch its variant surface glycoprotein (VSG) coat.

Site-specific recombination

Site-specific recombination is a process where specific DNA sequences are rearranged, leading to changes in the expressed antigens. This mechanism is used by Borrelia burgdorferi, the causative agent of Lyme disease, to vary its outer surface proteins.

Hypermutation

Hypermutation involves rapid mutations in the genes encoding surface antigens. This is a common strategy in RNA viruses such as influenza and HIV, where the high mutation rate of the viral genome leads to frequent changes in the antigenic properties of the virus.

Epigenetic regulation

Epigenetic changes, such as DNA methylation and histone modification, can also lead to antigenic variation by altering the expression of surface antigen genes without changing the underlying DNA sequence. This mechanism is observed in Plasmodium falciparum, the parasite responsible for malaria.

Biological significance

Antigenic variation allows pathogens to:

Evade the host's immune system by altering the antigens that are recognized by antibodies and T cells.
Prolong infection and increase the chances of transmission to new hosts.
Adapt to different host environments and immune pressures.

Examples in pathogens

Trypanosoma brucei

The African trypanosome, Trypanosoma brucei, is a protozoan parasite that causes African sleeping sickness. It uses antigenic variation to switch its VSG coat, allowing it to evade the host's immune response.

Plasmodium falciparum

Plasmodium falciparum, the most virulent species of malaria-causing parasites, uses antigenic variation to alter the expression of PfEMP1 proteins on the surface of infected red blood cells, helping it avoid immune detection.

Neisseria gonorrhoeae

Neisseria gonorrhoeae, the bacterium responsible for gonorrhea, undergoes antigenic variation of its pili and outer membrane proteins to escape immune surveillance.

Related pages

Gallery

Mechanisms of VSG switching in Trypanosoma brucei.
Mutation effects on HIV gp120 binding.

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-'''Aralkylamine N-acetyltransferase''' ('''AANAT''') is an [[enzyme]] that is involved in the [[biochemical]] process of [[melatonin]] synthesis. It is a key regulator in the production of melatonin, a hormone that plays a crucial role in regulating the [[circadian rhythm]] in many organisms, including humans.
+{{Short description|Overview of antigenic variation in pathogens}}
+{{Use dmy dates|date=October 2023}}
-== Function ==
+'''Antigenic variation''' is a mechanism by which an infectious organism alters its surface proteins in order to evade a host immune response. This process is crucial for the survival of many pathogens, allowing them to persist in the host and cause chronic infections. Antigenic variation is a common strategy among [[viruses]], [[bacteria]], and [[protozoa]].
-Aralkylamine N-acetyltransferase is responsible for the acetylation of [[serotonin]] into N-acetylserotonin, the immediate precursor of melatonin. This reaction is the penultimate step in the synthesis of melatonin from tryptophan. The enzyme is found in the [[pineal gland]], and its activity is regulated by a circadian rhythm, with the highest levels occurring at night.
+==Mechanisms==
+Antigenic variation can occur through several mechanisms, including:
-== Structure ==
+===Gene conversion===
+Gene conversion involves the replacement of one gene segment with another, leading to the expression of a different antigenic variant. This mechanism is well-studied in the [[African trypanosome]], which uses gene conversion to switch its variant surface glycoprotein (VSG) coat.
-The human AANAT enzyme is a monomer composed of 207 [[amino acids]]. It has a molecular weight of approximately 23 kDa. The enzyme contains a conserved acetyl-CoA binding site and a substrate binding site, which are crucial for its function.
+===Site-specific recombination===
+Site-specific recombination is a process where specific DNA sequences are rearranged, leading to changes in the expressed antigens. This mechanism is used by [[Borrelia burgdorferi]], the causative agent of [[Lyme disease]], to vary its outer surface proteins.
-== Clinical significance ==
+===Hypermutation===
+Hypermutation involves rapid mutations in the genes encoding surface antigens. This is a common strategy in [[RNA viruses]] such as [[influenza]] and [[HIV]], where the high mutation rate of the viral genome leads to frequent changes in the antigenic properties of the virus.
-Alterations in the function of AANAT can lead to a variety of disorders, including [[sleep disorders]], [[mood disorders]], and certain types of [[cancer]]. For example, low levels of AANAT and melatonin have been associated with [[insomnia]] and [[depression]]. In addition, some studies have suggested that AANAT may play a role in the development of [[breast cancer]] and [[prostate cancer]], possibly due to its role in regulating melatonin levels.
+===Epigenetic regulation===
+Epigenetic changes, such as DNA methylation and histone modification, can also lead to antigenic variation by altering the expression of surface antigen genes without changing the underlying DNA sequence. This mechanism is observed in [[Plasmodium falciparum]], the parasite responsible for [[malaria]].
-== See also ==
+==Biological significance==
+Antigenic variation allows pathogens to:
-* [[Melatonin]]
+* Evade the host's [[immune system]] by altering the antigens that are recognized by [[antibodies]] and [[T cells]].
-* [[Serotonin]]
+* Prolong infection and increase the chances of transmission to new hosts.
-* [[Pineal gland]]
+* Adapt to different host environments and immune pressures.
-* [[Circadian rhythm]]
-== References ==
+==Examples in pathogens==
-<references />
+===Trypanosoma brucei===
+The African trypanosome, ''[[Trypanosoma brucei]]'', is a protozoan parasite that causes [[African sleeping sickness]]. It uses antigenic variation to switch its VSG coat, allowing it to evade the host's immune response.
-[[Category:Enzymes]]
+===Plasmodium falciparum===
-[[Category:Biochemistry]]
+''[[Plasmodium falciparum]]'', the most virulent species of malaria-causing parasites, uses antigenic variation to alter the expression of [[PfEMP1]] proteins on the surface of infected red blood cells, helping it avoid immune detection.
-[[Category:Neuroscience]]
-[[Category:Sleep]]
+===Neisseria gonorrhoeae===
-[[Category:Cancer]]
+''[[Neisseria gonorrhoeae]]'', the bacterium responsible for [[gonorrhea]], undergoes antigenic variation of its pili and outer membrane proteins to escape immune surveillance.
-{{medicine-stub}}
+==Related pages==
+* [[Immune evasion]]
+* [[Pathogen]]
+* [[Vaccine development]]
+* [[Molecular biology]]
+==Gallery==
+<gallery>
+File:Mechanisms_of_VSG_switching2.png|Mechanisms of VSG switching in ''Trypanosoma brucei''.
+File:Mutation_outside_b12_epitope_affects_binding_of_b12_to_monomeric_gp120.jpg|Mutation effects on HIV gp120 binding.
+</gallery>
+[[Category:Microbiology]]
+[[Category:Immunology]]
+[[Category:Infectious diseases]]