Blood-depressing substance-1 (BDS-1), also known as kappa-actitoxin-Avd4a, is a polypeptide found in the venom of the

snakelocks anemone The snakelocks anemone (''Anemonia viridis'') is a sea anemone found in the eastern Atlantic Ocean and the Mediterranean Sea. The latter population is however sometimes considered a separate species, the Mediterranean snakelocks anemone (''Anem ...

''Anemonia sulcata''. BDS-1 is a neurotoxin that modulates voltage-dependent

potassium channels Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

, in particular Kv3-family channels, as well as certain

sodium channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...

. This polypeptide belongs to the sea anemone type 3 toxin peptide family.

Etymology

BDS-1 brings about a decrease in blood pressure by blocking Kv3 potassium channels. Thus, this protein is named after its antihypertensive function.

Sources

BDS-1 is a toxin secreted by the nematocyst of '' Anemonia sulcata'' (Mediterranean snakelocks sea anemone).

Chemistry

BDS-1 is a 43 amino acids long polypeptide chain, which consists of six cysteines linked by three

disulfide In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

bridges. The secondary structure of BDS-1 possesses three-stranded antiparallel

β-sheets The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

, along with one more short antiparallel β-sheet at its N-terminus. When viewed along the polypeptide strand, its structure showa a right-handed twist. BDS-1 shares structural homology with the toxin BDS-2, which belongs to the same type-3 peptide family. It also displays around 24–26% identity with toxins AsI (ATX-I), AsII (ATX-II), and AsV (ATX-V) from ''Anemonia sulcata'' and AxI (AP-A) from ''

Anthopleura xanthogrammica ''Anthopleura xanthogrammica'', or the giant green anemone, is a species of intertidal sea anemone of the family Actiniidae. Other common names for this anemone include green surf anemone, giant green sea anemone, green anemone, giant tidepo ...

''.

Target

BDS-1 is an inhibitor of the fast inactivating Kv3-family channels, including Kv3.1, Kv3.2 and Kv3.4 channels. Additionally, BDS-1 affects the inactivation of voltage-gated sodium channels,

Nav1.1 Sodium channel protein type 1 subunit alpha (SCN1A), is a protein which in humans is encoded by the ''SCN1A'' gene. Gene location The SCN1A gene is located on chromosome 2 of humans, and is made up of 26 exons spanning a total length of 6030 nu ...

Nav1.3 Sodium channel, voltage-gated, type III, alpha subunit (SCN3A) is a protein that in humans is encoded by the ''SCN3A'' gene. Function Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit wi ...

, Nav1.6 and

Nav1.7 Nav1.7 is a sodium ion channel that in humans is encoded by the ''SCN9A'' gene. It is usually expressed at high levels in two types of neurons: the nociceptive (pain) neurons at dorsal root ganglion (DRG) and trigeminal ganglion and sympathetic g ...

Mode of action

BDS-1 modifies the voltage-dependent gating properties of Kv3 potassium channels by binding to the voltage sensitive domains on S3b and S4 subunits. The toxin elicits a depolarizing shift in the conductance-voltage relation, making it more difficult to open, and slows both the activation and inactivation kinetics of these ion channels. In addition, BDS-1 enhances the current flowing through several voltage-gated sodium channels. The toxin binds to the S3-S4 linker of domain IV and slows the inactivation of the channel, resulting in increased current upon depolarization. BDS-1 has a very strong potency for the human

channel. In mice, BDS-1 slows the inactivation of

channels but has smaller effects on the inactivation of

and Nav1.6 channels. This is probably due to a different channel sensitivity for the toxin.

Toxicity

By targeting Kv3.1a channels, BDS-1 concentrations at or above 3 μM are toxic to mouse fibroblasts.

References

{{Reflist Ion channel toxins Sea anemone toxins Neurotoxins