Cryo-EM and MD simulations reveal the mechanism by which the potent neurotoxin α-latrotoxin forms calcium-permeable membrane pores.
The black widow spider is one of the most feared spider species. Its venom is a cocktail of seven different toxins that attack the nervous system. These so-called latrotoxins specifically paralyze insects and crustaceans. However, one of these toxins, α-latrotoxin, specifically targets vertebrates and is toxic to humans. It disrupts the transmission of nerve signals, leading to its harmful effects.
As soon as α-latrotoxin binds to specific receptors of the synapses – the contacts between nerve cells or between nerve cells and muscles – calcium ions flow uncontrollably into the presynaptic membranes of the signaling cells. This induces the release of neurotransmitters, triggering strong muscle contractions and spasms.
Complexity of the Process
Despite the apparent simplicity of this process, there is a highly complex mechanism behind it. Scientists at the University of Münster (Germany) have now deciphered the structure of α-latrotoxin before and after membrane insertion at near-atomic resolution.
In order to better understand the mechanism of calcium influx into the presynaptic membrane, experts from the Center for Soft Nanoscience at the University of Münster, headed by Prof Christos Gatsogiannis (Institute of Medical Physics and Biophysics) and Prof Andreas Heuer (Institute of Physical Chemistry), used high-performance cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) computer simulations.
Transformation of the Toxin
They showed that the toxin undergoes a remarkable transformation when it binds to the receptor. Part of the toxic molecule forms a stalk that penetrates the cell membrane like a syringe. As a special feature, this stalk forms a small pore in the membrane that functions as a calcium channel. MD simulations revealed that calcium ions can flow into the cell through a selective gate located on the side directly above the pore.
Thanks to these results, researchers now better understand how α-latrotoxin works. “The toxin mimics the function of the calcium channels of the presynaptic membrane in a highly complex way,” explains Christos Gatsogiannis. “It therefore differs in every respect from all previously known toxins.” The new findings open up a wide range of potential applications; latrotoxins have considerable biotechnological potential, including the development of improved antidotes, treatments for paralysis, and new biopesticides.
The research results have just been published in the journal Nature Communications. In previous work, the research group led by Christos Gatsogiannis had already deciphered the structure of insect-specific latrotoxins in the venom of the black widow spider before inserting into the membrane.
Reference: “Structural basis of α-latrotoxin transition to a cation-selective pore” by B. U. Klink, A. Alavizargar, K. S. Kalyankumar, M. Chen, A. Heuer and C. Gatsogiannis, 3 October 2024, Nature Communications.
DOI: 10.1038/s41467-024-52635-5
The study was funded by the German Research Foundation.
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43 Comments
This article should point out that although toxic to humans the black widow doesn’t emit enough to kill a human, It usually isn’t even serious enough to warrant a hospital or doctor visit.
Spiders, black widow spiders in particular have a bad reputation that needs to be undone. Male black widows cannot even break the skin of a human, and the females are not aggressive AT ALL.
Just like most insects they are beneficial and misunderstood.
My sister died 15 years ago from a black widow bite on the ankle. She developed an abscess in her spine neck area.
That is impossible. It is a scientific fact black widows are unable to kill an average size adult human. A small infant possibly though unlikely but an average size human not at all.
It’s also a scientific fact that if a full grown adult gets bitten while immunocompromised, they absolutely can and do die from it. Any weakness, illness or slowly brewing tooth infection can increase the severity of the effects. Individual tolerance level is another factor. A bite for one person could be pretty noneventful but could leave someone else hallucinating & awake for 5 days from unbearable agony.
The amount of venom they choose to inject is determined by maturity and level of fear. They have a limited supply and it takes time to restore it. In that time, they are kind of defenseless. They cant use what little they’ve built up and start all over again. They have no choice but to be selective. The youngsters though, don’t have the experience to make that judgment call to only use a little or none at all. So instead, they go allll in. They carry the same capacity for the venom regardless of size. It’s just that the babies use so much more of their venom than their older counterparts. The s smaller they are, the worse it is for us.
Kill it with fire!
There is always an exception to the rule. We don’t know everything about anything !
I was bitten by a black widow on my calf when I was 12 at 56 I can tell you it feels like someone holding a little cigarette on your skin. Like fire
There hasn’t been a confirmed death from a Black Widow but in just over 40 years. Dishonest fear mongering of a spider that already gets an unnecessarily bad rap. I’m so tired of journalism these days.
This specific spider is truly, my biggest fear in life. I literally can’t even hear someone say it’s name, or read it to myself because it truly send physical pain throughout my entire body. It’s a true phobia. I have horrible nightmares about them after seeing Charlotte’s Web because that spider, Charlotte, looks like one of them. Misunderstood, or not… They absolutely terrify me!
Fear mongering journalism doesn’t help when they use words like “Deadly” despite not a single person dying from its venom in 40 years. You have a FAR better chance of dying from lightning.
I was bit by a black widow spider in march of 2924 and I went into cardiac arrest at the ER .
2024
My grandfather when young, was bitten on the tip of the penis by a black widow spider, while using the outhouse. He recalled the terrible pain and muscle cramps. He also joked about being the talk of the community because of the swelling.
Gasp!!! That sounds more than a little dangerous to me!!! I hope you’re ok
This is the end result of 4yrs of trump,his stupid orange makeup is infiltrating drinking water in certain parts of the world!
get a life for God sake imbecile
I hope you can’t vote because you lack the intelligence needed to vote for the best candidate and please don’t leave comments that show how low your intelligence is because it’s sad knowing there is people among us whose intelligence is lower then a slug. You slug!
A Time Traveler Kool 👍
You’d be the first person to die from a Black widow bite in 40 years.
Black widow spider venom is 15 times more poisonous than a rattlesnake
Please list your sources. Not because I don’t believe it, but because I must have a reason to believe it.
You can’t spell lie without belief. Use logic to figure it out. We tend to give creedence to big and well respected names but they aren’t always right
America I’m schedule we want sorry but this is too important how will you feel watching Donald Trump take the oath of office that he’s already broken. We are already embarrassingly and ridiculously losing world respect and historic Idiocracy for us even allowing this travesty to get this far….. DON’T DO IT!!!!
We don’t need your TDS while trying to do research on important health and medical issues.
As an Australian observer Trump may be the last leader against a flood of globalist Marxist psychopaths
5 times more venomous. There’s a difference. Venom is what creatures used to inject and Harm other creatures. Poison is what creatures used to defend against being eaten or harmed by other creatures.
Thats a very good philosophical and straight forward explanation I think
I always say “If it bites you and you die, it’s venomous. If you bit It and you die, it’s poisonous.”
I was just going to say that ….
Thank you for your research on this important issue. I lived through an infestation of black widow spiders in a garage and home. It was sheer Hell and very expensive to combat. At times I has to sleep in my car, or at a friend’s home, or in a motel (for months), but came back to my home every day to combat the problem. The female black widow can produce 200 eggs. I vacuumed large quantities of baby widows off my popcorn ceilings on two stories of the home. Kill any Black Widow you see, to protect your home, your health, and your survival. They DO in fact become aggressive within your home when you are cleaning. The adult Widows move very fast and know where to position themselves and their webs, such as on the ceiling right over your work desk, repeatedly. When a young widow on a ceiling is dying from professional poison in the home, it does something eerie, called ballooning, which is hard to forget. Widows are NOT docile when trying to take over your own indoor habitat. In cold weather they want into your home. Kill them before they get into your home. In between professional poisonings, keep a spray bottle of white vinegar as well as Terro Spider killer, near you. Wear boots and long pants and a windbreaker with a hood.
I’ve been bitten on four different occasions and each time was unpleasant but never really life threatening.
I’ve got skull spiders in my house ,invasive, probably from a trip I took to Thailand. They apparently become the dominant insect as,I never see any other criteria in ,under or around since they have arrived. I believe they are harmless to humans,are extremely fragile, but are deadly to all others insects
“As soon as α-latrotoxin binds to specific receptors of the synapses – the contacts between nerve cells or between nerve cells and muscles – calcium ions flow uncontrollably into the presynaptic membranes of the signaling cells. This induces the release of neurotransmitters, triggering strong muscle contractions and spasms.”
This reminds me of psychiatry in how they say its a chemical imbalance. Somehow I dont buy that buy that but in some instances I do
Just how close is the relationship between the American black widow spider and the Australian Redback spider,they appear to be very similar (online answer if you know). Ron
Or are they the same spider but just with a different name?
They are both belong to the Black Widow spider family, as does the Brown Window spider from Australia. The Black Widow and Redback look identical, twins from different country. 😆
I survived a Brown Recluse spider bite without needing hospitalization; I may have been bitten by a Black Widow spider but I cannot guarantee it; I have been bitten by other unknown creatures. Chances are, if you got bit by a really poisonous spider, unless it releases enough venom to kill you, the real killer is the allergy to the venom rather than just the amount.
I read in an old National Geographic magazine like 1930s at the library that an average of one man a week died from a black widow bite in the U. S.
Well, by ‘unknown creatures’ I meant other spiders that I don’t know the breed of. I didn’t see them once it happened, but I know a spider bite once I see one.
I have caught and kept a black widow spider had her for a year she got huge I. Fed her alot I think they are bad ass looking and scary looking and I didn’t know that they shed there skin like A snake cool. Huh? Sorry for your bad experience with them they just trying to survive and sorry but trump has done some lame and pompous things but he loves America and would do so much to help get our country back on track if given the chance…he has been under attack by fbi and from Hillery and nobody’s got in trouble or gone to jail for lies tampering with evidence that directly impacted the election and Biden should be held accountable he is a crook had his hand in Chinese and Russian pockets our government and democracy is in serious trouble if not doom by all the greedy lies and corruption nobody’s getting fired or jail even if trump is the worst person on earth the people who lied and forged documents need to get punished or our country is over … The secret service agents that opened there mouths against our president fired or jailed we must. Respect our president even I did not have sexy relationship with that woman got respected after lies so stop hating trump give him a chance I don’t see why he would want to be president again he already had money and power he has heart and can sees nobody but him can stop the greedy America needs to hit the reset button..,…thanks matk
I used to have a Black Widow spider, too. I kept her in a jar. I called her Hillary.
I was bit by a Black Widow in 2016 while out chopping Wood. I had a large purple/black/red ring about the size of my hand and the cwnter of the bite area was bruised in color.
I was severely sick for more than 5 weeks. I also went to the emergency room 3 times and each time they told me I had the flu. I was in cold sweats with oily skin every night for that entire time. My muscles ached throughout my body and I felt sick to my stomach.
When I thought I was well about 6 months later I started realizing something severely was wrong with me because ai started having sharp pain shooting from my inner ear to my lower jawbone, down my neck, and into my heart. I felt like I was literally going to die each time the attack took place. I had an attack at home depo while shopping with my 6 year old and literally panicing because I thought I was going to die on the spot and leave my son alone.
I then finally found a specialist in the natural remedies and was tested for many things snd it turned out I was given a couple presents from that Black Widow. The doctor asked me if I knew I had been bit by a black widow and I told him my story. He then found that the spider gave me LimeDisease and 3 other bacterial infections. Each backeria infected my inner ear, my testicles, and my heart.
I was treated and free from the pain, but sadly I was bitten again by another spider and infected with LimeDisease again.
However, since I had been treated once before, it was easier to treat the second time around.
The black widow bite itself was very painful and I had no idea that you can get other sickness from such bites and so be aware of the possibility of it being more than just that bite.