Complement system impairing toxin

The complement system is an intrinsic part of the immune system, with important functions in both innate and adaptive immunity. The complement system consists of approximately twenty plasma proteins as well as numerous receptors and regulatory proteins on the membranes of host cells.

Activation of the complement system occurs through three pathways, the classical pathway , the alternative pathway (Fig.1) and the lectin pathway . All of these pathways share a similar molecular
architecture in that an initial recognition event is amplified by a succession of proteolytic enzymes in a cascade-like fashion, resulting in the generation of numerous biologically active complement activation products.
One activation product of the complement system is the macromolecular membrane attack complex (MAC) , which inserts itself into target membranes, leading to the impairment of membrane function and physical destruction of targets including viruses, bacteria, parasites and tumor cells. Another activation product is C3b which attaches itself covalently to cells, immune complexes and other particles, a process called opsonization. Opsonization tags cells and particles for removal by phagocytes. Further products of proteolytic degradation of C3b (iC3b, C3dg, C3d) are recognized by specific receptors on various immune cells, and have important functions in the regulation of the adaptive immune response. Last but not least, the anaphylatoxins C3a and C5a exhibit important pro-inflammatory activities, such as degranulation of mast cells, increased vascular permeability, and chemotaxis and activation of neutrophils. Both anaphylatoxins are rapidly inactivated by the removal of a C-terminal arginine residue through the action of carboxypeptidase N. However the inactivated form of C5a, C5a-des-Arg, still exhibits its activity for neutrophils, making C5a a particularly powerful pro-inflammatory peptide (reviewed in Vogel et al., 2010, and references therein).

Figure 1: The classical and alternative complement pathways. (Image from Wikimedia / licensed under Creative Commons).

Complement system impairing toxins target or mimic several complement system proteins. Only a few of them have had their activity specifically described. For example, snake venom complement C3 homologs are structural and functional analogs of complement component C3b. The snake venom serine proteinase flavoxobin independently cleaves endogenous C3 and kick-starts the complement cascade, the cobra metalloproteinase oxiagin prevents interaction of component C2 with C4b, while the cobra metalloproteinase atrase-B cleaves complement factors B, C6, C7, and C8. Most complement system impairing toxins have just been investigated for their effects on hemolytic complement activity, without having a more specific function described.

See also UniProt-keyword.

Venom protein entries in UniProtKB/Swiss-Prot

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18 entries grouped by species

2 entries

Austrelaps superbus (Lowland copperhead snake) (Hoplocephalus superbus)

VCO31_AUSSU A.superbus venom factor 1 (AVF-1) (CVF-like) (Complement C3 ... Venom complement C3 homolog ...
VCO32_AUSSU A.superbus venom factor 2 (AVF-2) (CVF-like) (Complement C3 ... Venom complement C3 homolog ...

1 entry

Bothrops asper (Terciopelo)

"Bothrops asper" VenomZone page
VM1B1_BOTAS Snake venom metalloproteinase BaP1 (SVMP) (EC 3.4.24.-) ... Venom metalloproteinase (M12B) ...

2 entries

Bothrops pirajai (Piraja's lancehead)

Select_allDeselect_all "Bothrops pirajai" VenomZone page
VSP27_BOTPI Thrombin-like enzyme BpirSP27 (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...
VSP41_BOTPI Thrombin-like enzyme BpirSP41 (SVTLE) (EC 3.4.21.-) ... Peptidase S1 family, Snake venom ...

4 entries

Cerberus rynchops (Dog-faced water snake)

FCNV1_CERRY Ryncolin-1 Ficolin lectin family, Veficolin ...
FCNV2_CERRY Ryncolin-2 Ficolin lectin family, Veficolin ...
FCNV3_CERRY Ryncolin-3 Ficolin lectin family, Veficolin ...
FCNV4_CERRY Ryncolin-4 Ficolin lectin family, Veficolin ...

1 entry

Crotalus adamanteus (Eastern diamondback rattlesnake)

"Crotalus adamanteus" VenomZone page
VCO3_CROAD Venom factor (VF) (CVF-like) (Complement C3 homolog) [Cleaved ... Venom complement C3 homolog ...

1 entry

Deinagkistrodon acutus (Hundred-pace snake) (Agkistrodon acutus)

VM3A2_DEIAC Zinc metalloproteinase recombinant fibrinogenase II (FIIa) (rF ... Venom metalloproteinase (M12B) ...

1 entry

Naja atra (Chinese cobra)

"Naja atra" VenomZone page
VM3B_NAJAT Zinc metalloproteinase-disintegrin-like atrase-B (EC 3.4.24.-) ... Venom metalloproteinase (M12B) ...

2 entries

Naja kaouthia (Monocled cobra) (Naja siamensis)

VCO3_NAJKA Cobra venom factor (CVF) (CVFk) (Complement C3 homolog) [Cleaved ... Venom complement C3 homolog ...
VM3_NAJKA Zinc metalloproteinase-disintegrin-like cobrin (EC 3.4.24.-) ... Venom metalloproteinase (M12B) ...

1 entry

Naja oxiana (Central Asian cobra) (Oxus cobra)

VM3_NAJOX Zinc metalloproteinase oxiagin (EC 3.4.24.-) (Snake venom ... Venom metalloproteinase (M12B) ...

1 entry

Ophiophagus hannah (King cobra) (Naja hannah)

VCO3_OPHHA Ophiophagus venom factor (OVF) (CVF-like) (Complement C3 ... Venom complement C3 homolog ...

1 entry

Protobothrops flavoviridis (Habu) (Trimeresurus flavoviridis)

VSP1_PROFL Thrombin-like enzyme flavoxobin (SVTLE) (EC ... Peptidase S1 family, Snake venom ...

1 entry

Varanus komodoensis (Komodo dragon)

FCNV1_VARKO Veficolin-1 Ficolin lectin family, Veficolin ...