{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:29:12Z","timestamp":1790796552016,"version":"4.1.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Helminths produce calreticulin (CRT) to immunomodulate the host immune system as a survival strategy. However, the structure of helminth-derived CRT and the structural basis of the immune evasion process remains unclarified. Previous study found that the tissue-dwelling helminth <jats:italic>Trichinella spiralis<\/jats:italic> produces calreticulin (TsCRT), which binds C1q to inhibit activation of the complement classical pathway. Here, we used x-ray crystallography to resolve the structure of truncated TsCRT (TsCRT<jats:sup>\u0394<\/jats:sup>), the first structure of helminth-derived CRT. TsCRT<jats:sup>\u0394<\/jats:sup> was observed to share the same binding region on C1q with IgG based on the structure and molecular docking, which explains the inhibitory effect of TsCRT on C1q-IgG\u2013initiated classical complement activation. Based on the key residues in TsCRT<jats:sup>\u0394<\/jats:sup> involved in the binding activity to C1q, a 24 amino acid peptide called P<jats:sup>TsCRT<\/jats:sup> was constructed that displayed strong C1q-binding activity and inhibited C1q-IgG\u2013initiated classical complement activation. This study is the first to elucidate the structural basis of the role of TsCRT in immune evasion, providing an approach to develop helminth-derived bifunctional peptides as vaccine target to prevent parasite infections or as a therapeutic agent to treat complement-related autoimmune diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1404752","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T05:02:22Z","timestamp":1713243742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Crystal structure of Trichinella spiralis calreticulin and the structural basis of its complement evasion mechanism involving 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