5ilt

Publication Abstract from PubMed

Antibodies provide a broad defense against a vast array of antigens; however, the structural features that contribute to this diverse antigen recognition vary in different vertebrates. In cows, a subset of antibodies have an exceptionally long third heavy-chain complementarity-determining region (CDR H3) that is highly variable in sequence and includes multiple cysteines. These long CDR H3s (up to 69 residues) fold into a long stalk atop which sits a knob domain that is located far from the antibody surface. We have determined crystal structures of three bovine Fabs to decipher the conserved and variable features of ultralong CDR H3s that lead to diversity in antigen recognition. Despite high sequence variability, the stalks adopt a conserved beta-ribbon structure, whereas the knob regions share a conserved beta sheet that serves as a scaffold for two connecting loops of variable length and conformation, as well as one conserved disulfide. Variation in patterns and connectivity of the remaining disulfides contribute to the structural diversity of the knob. The unusual architecture of these ultralong bovine CDR H3s for generating diversity is unique in adaptive immune systems and may inform efforts in antibody engineering.

Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies.,Stanfield RL, Wilson IA, Smider VV Sci Immunol. 2016 Jul 14;1(1):aaf7962. doi: 10.1126/sciimmunol.aaf7962. Epub 2016, Jun 23. PMID:28783675^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.