{"id":32613,"date":"2025-11-28T12:57:34","date_gmt":"2025-11-28T17:57:34","guid":{"rendered":"https:\/\/www.med.unc.edu\/biochem\/?p=32613"},"modified":"2025-11-28T13:08:31","modified_gmt":"2025-11-28T18:08:31","slug":"celebrating-maness-labs-latest-publication-in-the-journal-of-biological-chemistry","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/biochem\/news\/celebrating-maness-labs-latest-publication-in-the-journal-of-biological-chemistry\/","title":{"rendered":"Celebrating Maness lab\u2019s Latest Publication in The Journal of Biological Chemistry"},"content":{"rendered":"<p><span data-contrast=\"auto\">We are proud to announce that <a href=\"https:\/\/srclab.web.unc.edu\/\">Dr. Patricia F. Maness<\/a> and colleagues have published a groundbreaking article in <\/span><i><span data-contrast=\"auto\">The Journal of Biological Chemistry<\/span><\/i><span data-contrast=\"auto\"> titled, <\/span><b><span data-contrast=\"auto\">\u201cStructural interactions of ankyrin B with NrCAM and \u03b22 spectrin.\u201d<\/span><\/b><span data-contrast=\"auto\"> This research uses state-of-the-art AI-based molecular modeling to reveal how the 220 kDa isoform of Ankyrin B (AnkB)\u2014a scaffold protein encoded by the autism risk gene ANK2\u2014forms critical connections with the neuronal cell adhesion molecule NrCAM and \u03b22-spectrin. By validating these predicted interactions with targeted mutagenesis and co-immunoprecipitation experiments, the study pinpoints how specific missense mutations linked to ASD can disrupt AnkB\u2019s interactions and neuronal function. These findings not only deepen our understanding of neuronal connectivity and synapse development but also highlight potential molecular mechanisms contributing to ASD.<\/span><span data-ccp-props=\"{}\">\u00a0<\/span><\/p>\n<h2><span data-contrast=\"auto\">A note from the <\/span><span data-contrast=\"auto\">first author<\/span><span data-ccp-props=\"{}\">\u00a0<\/span><\/h2>\n<figure id=\"attachment_32587\" class=\"thumbnail wp-caption alignnone\" style=\"width: 225px\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-32587 size-medium\" src=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2021\/10\/Ve-photo-215x300.png\" alt=\"Venkata Reddy Chirasani\" width=\"215\" height=\"300\" srcset=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2021\/10\/Ve-photo-215x300.png 215w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2021\/10\/Ve-photo.png 522w\" sizes=\"auto, (max-width: 215px) 100vw, 215px\" \/><figcaption class=\"caption wp-caption-text\">First author, Venkat R Chirasani, Ph.D., Assistant Professor, Director, R. L. Juliano Structural Bioinformatics Core<\/figcaption><\/figure>\n<p><span data-contrast=\"auto\">In this work, we focused on Ankyrin B (AnkB) \u2014 a scaffold protein encoded by the high-confidence autism spectrum disorder (ASD) risk gene ANK2 \u2014 and investigated its molecular interactions with the cytoplasmic domain of the L1-family cell adhesion molecule NrCAM and with \u03b22\u2011spectrin. These findings advance our mechanistic understanding of how AnkB links neuronal cell-adhesion molecules and the spectrin-actin cytoskeleton to regulate dendritic spine dynamics and excitatory synapse maturation.<\/span><span data-ccp-props=\"{}\">\u00a0<\/span><\/p>\n<h2><span data-contrast=\"none\">Abstract<\/span><span data-ccp-props=\"{&quot;134245418&quot;:true,&quot;134245529&quot;:true,&quot;335559738&quot;:160,&quot;335559739&quot;:80}\">\u00a0<\/span><\/h2>\n<p><i><span data-contrast=\"auto\">Ank2 is a high confidence autism spectrum disorder (ASD) gene encoding the spectrin-actin scaffold protein Ankyrin B (AnkB). The 220 kDa isoform of AnkB has multiple functions including developmental spine pruning through L1 family cell adhesion molecules (L1-CAMs) and class 3 Semaphorins on dendrites of pyramidal neurons to achieve an appropriate excitatory balance in the neocortex. Molecular modeling employing AlphaFold was used to predict the structure and interactions of AnkB with the cytoplasmic domain of Neuron-glial Related L1-CAM (NrCAM), and with \u03b22-Spectrin. The validity of the models was assessed by analyzing protein-protein interactions by co-immunoprecipitation from HEK293 cell lysates after mutating key residues in AnkB predicted to impair these associations. Results revealed a pocket with critical residues in the AnkB membrane-binding domain that engages NrCAM at the conserved cytoplasmic motif \u2013 FIGQY. AlphaFold modeling of the AnkB\/\u03b22-Spectrin complex identified key interactions between the AnkB spectrin-binding domain and \u03b22-Spectrin repeats 14-15.\u00a0 Selected ASD-linked mutations in AnkB predicted to impact binding to NrCAM or \u03b22-Spectrin were then assayed for protein interactions. Maternally inherited ASD missense mutations AnkB A368G located in the NrCAM binding pocket and AnkB R977Q in the Zu5A subdomain disrupted associations with NrCAM and \u03b22-Spectrin, respectively. Moreover, AnkB A368G impaired the neuronal function of 220 kDal AnkB for Semaphorin 3F-induced spine pruning in mouse cortical neuron cultures. These new findings provide structural insights into the L1-CAM\/AnkB complex and the molecular basis of ASD etiology associated with AnkB missense mutations.<\/span><\/i><span data-ccp-props=\"{}\">\u00a0<\/span><\/p>\n<h2 data-ccp-border-bottom=\"1px solid #000000\" data-ccp-padding-bottom=\"1.3333333333333333px\">Citation<\/h2>\n<p data-ccp-border-bottom=\"1px solid #000000\" data-ccp-padding-bottom=\"1.3333333333333333px\"><span data-contrast=\"auto\">Chirasani, V. R., Haberman, V. A., Oldre, E. N., Webb, B. D., Pereira, E. B., Yang, W., &amp; Maness, P. F. (2025). <a href=\"https:\/\/doi.org\/10.1016\/j.jbc.2025.110872\">Structural interactions of ankyrin B with NrCAM and \u03b22 spectrin. <\/a><\/span><i><span data-contrast=\"auto\">Journal of Biological Chemistry<\/span><\/i><span data-contrast=\"auto\">, 301(1), 110872.<\/span><\/p>\n<figure id=\"attachment_31395\" class=\"thumbnail wp-caption alignnone\" style=\"width: 212px\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-31395 size-medium\" src=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2015\/06\/PM-202x300.jpg\" alt=\"Dr. Patricia Maness 2025 horse in background\" width=\"202\" height=\"300\" srcset=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2015\/06\/PM-202x300.jpg 202w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2015\/06\/PM-690x1024.jpg 690w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2015\/06\/PM-600x890.jpg 600w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2015\/06\/PM-560x831.jpg 560w, https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2015\/06\/PM.jpg 749w\" sizes=\"auto, (max-width: 202px) 100vw, 202px\" \/><figcaption class=\"caption wp-caption-text\">Dr. Patricia Maness, Professor<\/figcaption><\/figure>\n<p data-ccp-border-bottom=\"1px solid #000000\" data-ccp-padding-bottom=\"1.3333333333333333px\"><a href=\"https:\/\/srclab.web.unc.edu\/\">Maness lab website<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>We are proud to announce that Dr. Patricia F. Maness and colleagues have published a groundbreaking article in The Journal of Biological Chemistry titled, \u201cStructural interactions of ankyrin B with NrCAM and \u03b22 spectrin.\u201d This research uses state-of-the-art AI-based&#8230;<\/p>\n","protected":false},"author":41619,"featured_media":32616,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[10,179,13],"class_list":["post-32613","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-news_faculty","tag-news_postdoc-scholars","tag-news_students","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Celebrating Maness lab\u2019s Latest Publication in The Journal of Biological Chemistry | Biochemistry and Biophysics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/biochem\/news\/celebrating-maness-labs-latest-publication-in-the-journal-of-biological-chemistry\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Celebrating Maness lab\u2019s Latest Publication in The Journal of Biological Chemistry | Biochemistry and Biophysics\" \/>\n<meta property=\"og:description\" content=\"We are proud to announce that Dr. Patricia F. 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