• The allosteric modulation of complement c5 by knob domain peptides 

      Macpherson, Alex; Laabei, Maisem; Ahdash, Zainab; Graewert, Melissa Ann; Birtley, James R.; Schulze, Monika-Sarah E.D.; Crennell, Susan; Robinson, Sarah A.; Holmes, Ben; Oleinikovas, Vladas; Nilsson, Per H.; Snowden, James; Ellis, Victoria; Mollnes, Tom Eirik; Deane, Charlotte M.; Svergun, Dmitri I.; Lawson, Alastair D.G.; van den Elsen, Jean (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-02-11)
      Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3–6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. ...
    • A conformational change of complement C5 is required for thrombin-mediated cleavage, revealed by a novel ex vivo human whole blood model preserving full thrombin activity 

      Nilsson, Per; Johnson, Christina; Quach, Huy Quang; Macpherson, Alex; Durrant, Oliver; Pischke, Soeren; Fure, Hilde; Landsem, Anne; Bergseth, Grete; Schjalm, Camilla; Haugaard-Kedström, Linda M.; Huber-Lang, Markus; van den Elsen, Jean; Brekke, Ole-Lars; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-15)
      Thrombin activation of C5 connects thrombosis to inflammation. Complement research in whole blood ex vivo necessitates anticoagulation, which potentially interferes with the inflammatory modulation by thrombin. We challenged the concept of thrombin as an activator of native C5 by analyzing complement activation and C5 cleavage in human whole blood anticoagulated with Gly-Pro-Arg-Pro (GPRP), a peptide ...