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October 20, 2025<\/p>\n
3 min read<\/p>\n
Cells Have a Crystal Trigger That Makes Them Self-Destruct When Viruses Invade<\/p>\n
A special class of immune proteins protect us from pathogens but also drive inflammation and cell death<\/p>\n
By Viviane Callier edited by Tanya Lewis<\/span><\/p>\n A model showing proteins called death fold domains (green) telling a caspase enzyme (blue) to kill the cell after it has been compromised by pathogens.<\/p>\n Stowers Institute for Medical Research\/Tayla Miller<\/p>\n The immune system has a tough job: When a tiny virus invades one of our cells, that cell must detect it and, within minutes, decide what to do. If the cell quickly self-destructs, that will prevent the virus from spreading throughout the body. But such a response to a false alarm will mean the cell will die unnecessarily.<\/p>\n Now researchers have discovered that a special group of about 100 immune proteins hangs out inside every cell in the body, where these proteins do nothing but wait. Then, when a virus breaks in, it seeds a crystal, and the proteins instantly clump around it, forming a scaffold for enzymes known as caspases to activate and immediately initiate cell death. (The caspases must be brought together to kill the cell; it is their proximity to one another that activates them.) The kind of cell death caused by this mechanism is called pyroptosis, and unlike apoptosis (programmed cell death), it triggers inflammation.<\/p>\n \u201cWhat we found, in essence, is that the cells are literally waiting to die all the time,\u201d says Randal Halfmann, an associate investigator at the Stowers Institute for Medical Research. Halfmann oversaw the work, which was published in eLife in September.<\/p>\n If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.<\/p>\n Historically, scientists have studied proteins\u2019 folded structures to understand their function individually. But \u201cwe\u2019re in this explosion of discovery, realizing that these individual molecules that we\u2019ve studied so well are coming together into larger structures that are not bound by membranes,\u201d says D. Allan Drummond, a molecular biologist at the University of Chicago, who was not involved in the study. This new understanding has prompted \u201cnew kinds of ways of thinking about cellular function and decision-making by cells, new ways for them to store energy, and so on.\u201d<\/p>\n The study, which was done in living yeast cells and human cell lines, illustrates how proteins act collectively by forming a crystal that gathers caspases together to activate the cell death program and enable the cell to make a rapid life-or-death decision. It also provides an example of how solid protein clumps, which are typically believed to be pathological (such as in Alzheimer\u2019s disease), can be essential to function: \u201cIn order to be useful, their whole job is to be this irreversible, downhill, spontaneous reaction that allows the cell to make decisions that include killing the cell,\u201d Drummond says. The rapidity of the decision is key: if the cell relies on more traditional signaling pathways that activate genes in response to an infection, an agile virus could take control of the cell\u2019s protein-making machinery before the cell has a chance to respond.<\/p>\n Although structural biologists had studied this kind of protein behavior in test tubes, \u201cwhat was really lacking was: \u2018Does this really happen in the cell?\u2019\u201d says Bostjan Kobe, a protein structural biologist at the University of Queensland in Australia. \u201cThat\u2019s why [Halfmann\u2019s] work was really interesting\u2014because it came at the problem from a completely different angle.\u201d<\/p>\n Halfmann\u2019s team observed that these immune proteins typically remain soluble but that, given enough time\u2014over a lifespan\u2014they will spontaneously crystallize, misfiring in a way that leads to cell death and inflammation. \u201cWhat this means is that if you wait long enough, every cell will die via this mechanism because even if a virus doesn\u2019t get into the cell, it will happen at some frequency spontaneously,\u201d Halfmann says. (Of course, cells can die by other mechanisms, such as apoptosis, first.)<\/p>\n Halfmann\u2019s team quantified the driving force for these proteins to crystallize in different human cell types and found that their concentration is correlated with the rate of cell turnover in our body. For example, some blood cells are replaced every few days, whereas neurons often last a lifetime. The faster cells normally turn over, the more of these immune proteins they tend to have, suggesting that this process of spontaneous activation might be responsible for killing them.<\/p>\n These results suggest that these immune proteins might be contributing to the low-grade inflammation that accompanies aging. Finding ways to keep the proteins from crystallizing could potentially extend cells\u2019 lifespan and reduce aging-related inflammation, but the trade-off would be a weaker immune system, Halfmann says.<\/p>\n This feature of the immune system is very ancient. It is found in the earliest animals, such as sponges, and it even exists in bacteria, from which we likely inherited it. It is specifically found in some bacteria that live in tight-knit communities. \u201cIf you\u2019re a single-celled organism, there\u2019s no drive to kill yourself,\u201d Halfmann says. \u201cBut when you\u2019re part of a community and you\u2019re compromised by a phage [a virus that kills bacteria], then it absolutely makes sense to kill yourself because you\u2019re related to everybody around you, and that is where these proteins seem to have evolved.\u201d<\/p>\n If you enjoyed this article, I\u2019d like to ask for your support. Scientific American<\/span> has served as an advocate for science and industry for 180 years, and right now may be the most critical moment in that two-century history.<\/p>\n I\u2019ve been a Scientific American<\/span> subscriber since I was 12 years old, and it helped shape the way I look at the world. SciAm <\/span>always educates and delights me, and inspires a sense of awe for our vast, beautiful universe. I hope it does that for you, too.<\/p>\n If you subscribe to Scientific American<\/span>, you help ensure that our coverage is centered on meaningful research and discovery; that we have the resources to report on the decisions that threaten labs across the U.S.; and that we support both budding and working scientists at a time when the value of science itself too often goes unrecognized.<\/p>\n In return, you get essential news, captivating podcasts, brilliant infographics, can’t-miss newsletters, must-watch videos, challenging games, and the science world’s best writing and reporting. You can even gift someone a subscription.<\/p>\n There has never been a more important time for us to stand up and show why science matters. I hope you\u2019ll support us in that mission.<\/p>\n","protected":false},"excerpt":{"rendered":" October 20, 2025 3 min read Cells Have a Crystal Trigger That Makes Them Self-Destruct When Viruses Invade A special class of immune proteins protect us from pathogens but also drive inflammation and cell death By Viviane Callier edited by Tanya Lewis A model showing proteins called death fold domains (green) telling a caspase enzyme<\/p>\n","protected":false},"author":1,"featured_media":29317,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[58],"tags":[10185,7627,17332,17331,3317,6382],"class_list":{"0":"post-29316","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science","8":"tag-cells","9":"tag-crystal","10":"tag-invade","11":"tag-selfdestruct","12":"tag-trigger","13":"tag-viruses"},"_links":{"self":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/29316","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=29316"}],"version-history":[{"count":0,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/29316\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/media\/29317"}],"wp:attachment":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=29316"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=29316"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=29316"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}On supporting science journalism<\/h2>\n
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