{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:50:18Z","timestamp":1791291018236,"version":"4.3.0"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"abstract":"<jats:p>Cattle produce a subset of antibodies (Abs) with unique architecture. These immunoglobulins feature an ultralong CDR\u2010H3 (uCDR\u2010H3) composed of up to about 70 amino acids that protrudes from the scaffold and folds into a distinct stalk\u2010and\u2010knob structure. The knob is a disulfide\u2010rich mini\u2010domain that contains all paratope residues for antigen recognition. Due to their vast structural diversity and low molecular weight, cattle\u2010derived knob paratopes have emerged as promising building blocks for engineering next\u2010generation Abs. In this review, we discuss the structural features of uCDR\u2010H3 Abs alongside engineering strategies of cattle\u2010derived knob architectures, including stand\u2010alone knob peptides and knob engraftments to generate bispecific antibodies (bsAbs).<\/jats:p>","DOI":"10.1002\/1873-3468.70475","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:50:59Z","timestamp":1791287459000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Becoming the bull<\/i>\n                    : Structural insights and engineering strategies for ultralong\n                    <scp>CDR<\/scp>\n                    \u2010\n                    <scp>H3<\/scp>\n                    paratopes from cattle"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-1941","authenticated-orcid":false,"given":"Andreas","family":"Evers","sequence":"first","affiliation":[{"name":"Antibody 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Life Sciences, Technical University of Munich  Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4649-2843","authenticated-orcid":false,"given":"Stefan","family":"Zielonka","sequence":"additional","affiliation":[{"name":"Antibody Discovery and Protein Engineering NBE Technologies, Merck Healthcare KGaA  Darmstadt Germany"},{"name":"Biomolecular Immunotherapy Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2025.2583210","article-title":"From discovery to the clinic: structural insights, engineering options, clinical, and \u201cnext wave\u201d applications of camelid\u2010derived single\u2010domain antibodies","volume":"17","author":"Evers 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