[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-413245-105":59,"doc-detail-413245-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","lps-induced-structural-reorganization-and-polymerization-drive-noncanonical-inflammasome-activation","LPS-induced structural reorganization and polymerization drive noncanonical inflammasome activation","","LPS binding activates the noncanonical inflammasome by engaging murine caspase-11 and human orthologs caspase-4/5, yet the structural mechanism linking LPS recognition to caspase oligomerization has remained unclear. This work shows caspase-4/11 CARDs are intrinsically unstructured in resting conditions and adopt an α-helical conformation after LPS engagement. Hexa-acylated LPS promotes large CARD oligomers with eight or more protomers, while underacylated lipids drive smaller assemblies. Hydrophobic pockets required for LPS binding and interfacial contacts that enable oligomerization are mapped using HDX-MS and XL-MS, providing mechanistic insight into innate immune activation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/lps-induced-structural-reorganization-and-polymerization-drive-noncanonical-inflammasome-activation/413245/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/lps-induced-structural-reorganization-and-polymerization-drive-noncanonical-inflammasome-activation/413245.png","ImageObject",300,407,{"name":92,"@type":93},"RuangKosong","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main question addressed by the study?","Question",{"text":112,"@type":113},"How LPS binding structurally drives caspase-4/11 oligomerization and activation remains poorly understood, and the study aims to clarify this mechanism.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do caspase-4/11 CARDs change upon LPS engagement?",{"text":117,"@type":113},"The CARDs adopt a largely unstructured conformation in the resting state and transition into an α-helical conformation upon LPS binding, accompanied by CARD oligomerization.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the acyl chain number of LPS influence inflammasome activation?",{"text":121,"@type":113},"Hexa-acylated LPS induces formation of large CARD oligomers containing eight or more protomers, whereas underacylated lipids promote smaller assemblies that fail to trigger the same activation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},413245,1792417395,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962090883219,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Copyright o2026 The  \nAuthors,some rights  \nLPS-induced structural reorganization andpolymerization drive noncanonicalinflammasome activation  \nreserved;exclusive  \nlicensee American  \nAssociation for the  \nAdvancement of  \nScience.No claim to  \noriginal U.S.  \nGovernment Works.  \nChengliang Wang¹+,Philip Lacey²+,Tian Tian¹t,Evelyn Teran¹,Maham Liaqat³,Sonia Shivcharan¹,Patience Shumba¹,Jie He³,4,Vijay A.Rathinam¹,Vicki H.Wysocki²≠,Jianbin Ruan¹*  \nDistributed under a  \nCreative Commons  \nAttribution  \nThe noncanonical inflammasome,mediated by murine caspase-11and itshuman orthologs caspase-4 and caspase-  \nNonCommercial  \n5,detects intracellular lipopolysaccharide (LPS)and triggers pyroptotic cell death.Upon LPS binding through theiramino-terminal caspase activation and recruitment domains(CARDs),these inflammatory caspases oligomerizeand activate.However,how LPS binding drives caspase-4/11 activation remains unclear.Here,we show that cas-pase-4/11 CARDs are intrinsically unstructured in their resting state and adopt an α-helical conformation uponLPSengagement.This structural rearrangement promotes CARD oligomerization,with electron-capture charge reduc-tion-coupled native mass spectrometry and other techniques illustrating that hexa-acylated LPS induces the for-mation of large oligomers composed of eight or more protomers,whereas underacylated lipids trigger smallerassemblies.Using hydrogen-deuterium exchange mass spectrometry and cross-linking mass spectrometry,weidentified a hydrophobic cleft critical for LPS binding and potential intersubunit interfaces that facilitate oligomer-ization.These findings uncover key structural features underlying LPS recognition and activation of the noncanoni-cal inflammasome,providing mechanistic insight into an essential arm of the innate immune response.  \nLicense 4.0(CC BY-NC).  \nundergo oligomerization and activation,resulting in the proteo-lytic cleavage of downstream targets,including the pore-formingprotein gasdermin D(GSDMD)and the precursor cytokine pro-interleukin-18(pro-IL-18)(12,15-20).Cleaved GSDMD formsmembrane-inserted pores that drive pyroptotic cell death and pro-mote the release of mature cytokines and other intracellular inflam-matory mediators(17,21-26).Although this pathway plays a criticalrole in antimicrobial host defense,its dysregulation has also beenimplicated in the pathogenesis of various autoinflammatory and in-fectious diseases(27).  \n# INTRODUCTION\n\nThe innate immune system serves as the first line of defense againstmicrobial invasion by initiating rapid inflammatory responses thatrestrict pathogen dissemination,promote tissue repair,and recruiteffectorimmune cells.Central to these responses are pattern recogni-tion receptors(PRRs)(1,2),which detect conserved microbial com-ponents known as pathogen-associated molecular patterns(PAMPs)and endogenous damage-associated molecular patterns(DAMPs)released from damaged or dying cells(3,4).Among these molecularpatterns,lipopolysaccharide(LPS),which is a key structural compo-nent of the outer membrane of Gram-negative bacteria,is one of themost potent and well-characterized PAMPs.  \nDespite the physiological significance of the noncanonical in-flammasome,the molecular mechanisms by which LPS bindingstructurally drives caspase-4/11 oligomerization and activation re-main poorly understood.Here,we demonstrate that the CARDs ofcaspase-4/11 adopt a largely unstructured conformation in theirresting state and transition into anα-helical conformation upon LPSbinding.This conformational shift is accompanied by the oligomer-ization of the CARDs.Hexa-acylated LPS promotes the assembly oflarge CARD oligomers containing eight or more protomers,where-as underacylated lipids induce the formation of smaller assemblies.Using hydrogen-deuterium exchange mass spectrometry(HDX-MS)and cross-linking mass spectrometry(XL-MS),we identified ahydrophobic pocket critical for LPS binding as well as potential in-terfacial contacts that mediate CAR","cbCainqsz1tgHnNI","https://ap.wps.com/l/cbCainqsz1tgHnNI","pdf",11101145,14,"English","# INTRODUCTION\n# RESULTS\n## Acyl chain number of LPS dictates caspase-4/11 CARD oligomerization","[{\"question\":\"What is the main question addressed by the study?\",\"answer\":\"How LPS binding structurally drives caspase-4/11 oligomerization and activation remains poorly understood, and the study aims to clarify this mechanism.\"},{\"question\":\"How do caspase-4/11 CARDs change upon LPS engagement?\",\"answer\":\"The CARDs adopt a largely unstructured conformation in the resting state and transition into an α-helical conformation upon LPS binding, accompanied by CARD oligomerization.\"},{\"question\":\"How does the acyl chain number of LPS influence inflammasome activation?\",\"answer\":\"Hexa-acylated LPS induces formation of large CARD oligomers containing eight or more protomers, whereas underacylated lipids promote smaller assemblies that fail to trigger the same activation.\"}]","LPS-induced structural reorganization and polymerization drive noncanonical inflammasome activation | PDF",1790594250,35]