{"id":49357,"date":"2025-11-23T02:40:28","date_gmt":"2025-11-23T01:40:28","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/23\/the-c-terminal-domain-of-staphylococcus-aureus-efb-recruits-fhr-2-to-c3b-synergistically-inhibiting-the-terminal-complement-pathway\/"},"modified":"2025-11-23T02:40:28","modified_gmt":"2025-11-23T01:40:28","slug":"the-c-terminal-domain-of-staphylococcus-aureus-efb-recruits-fhr-2-to-c3b-synergistically-inhibiting-the-terminal-complement-pathway","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/23\/the-c-terminal-domain-of-staphylococcus-aureus-efb-recruits-fhr-2-to-c3b-synergistically-inhibiting-the-terminal-complement-pathway\/","title":{"rendered":"The C-terminal domain of Staphylococcus aureus Efb recruits FHR-2 to C3b, synergistically inhibiting the terminal complement pathway"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Nov 22:vkaf316. doi: 10.1093\/jimmun\/vkaf316. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>The extracellular fibrinogen-binding protein (Efb) is one of nearly a dozen proteins secreted by Staphylococcus aureus to inhibit complement activation or amplification. The C-terminal domain of Efb (Efb-C) forms a high-affinity interaction with the thioester-containing domain of C3b (TED\/C3d), thereby blocking formation of the C3 proconvertase complex through an allosteric mechanism. However, further functional consequences of Efb-C binding to C3b remain unexplored. Here, we identified a previously unknown interaction between Efb-C, C3b, and the complement regulatory molecule FHR2 (factor H-related protein 2). Since the FHR2\/C3b interaction is centered upon the 2 C-terminal-most domains of FHR2 (FHR2[3-4]) and the TED\/C3d domain of C3b, we tested whether Efb-C could influence the FHR2(3-4)\/C3d interaction. We observed a significant enhancement of FHR2(3-4)\/C3d binding in the presence of Efb-C. We studied the FHR2(3-4)\/C3d\/Efb-C complex by X-ray crystallography and found that Efb-C forms few direct interactions with FHR2(3-4). Yet, the presence of Efb-C also enhanced binding of FHR2(3-4) and full-length FHR2 to C3b, suggesting that the effect of Efb-C on the FHR2\/C3b interaction arises from increased accessibility of the FHR2-binding site. We found that enhanced FHR2 binding did not impact the rate of C3 convertase formation more than Efb-C alone, nor did it impart decay acceleration or cofactor activity. However, we observed potent, synergistic inhibition of complement downstream of C5 activation by Efb-C and FHR2 but not by Efb-C and FHR2(3-4). Our results show that Efb-C binding to C3b exerts additional inhibitory effects on the central complement components beyond blocking formation of the C3 proconvertase alone.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41273729\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20251122204028&amp;v=2.18.0.post22+67771e2\">41273729<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf316\">10.1093\/jimmun\/vkaf316<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Nov 22:vkaf316. doi: 10.1093\/jimmun\/vkaf316. Online ahead of print. ABSTRACT The extracellular fibrinogen-binding protein (Efb) is one of nearly a dozen proteins secreted by Staphylococcus aureus to inhibit complement activation or amplification. The C-terminal domain of Efb (Efb-C) forms a high-affinity interaction with the thioester-containing domain of C3b (TED\/C3d), thereby blocking formation of &#8230; <a title=\"The C-terminal domain of Staphylococcus aureus Efb recruits FHR-2 to C3b, synergistically inhibiting the terminal complement pathway\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/11\/23\/the-c-terminal-domain-of-staphylococcus-aureus-efb-recruits-fhr-2-to-c3b-synergistically-inhibiting-the-terminal-complement-pathway\/\" aria-label=\"Read more about The C-terminal domain of Staphylococcus aureus Efb recruits FHR-2 to C3b, synergistically inhibiting the terminal complement pathway\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-49357","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/49357","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=49357"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/49357\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=49357"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=49357"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=49357"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}