Fig. 4: The von Willebrand type D (vWD) and C-terminal cystine knot (CTCK) domains in Vg and in functionally unrelated homologues.
a Structures of vWD (including the accompanying modules C8-3, TIL3 and E3) and CTCK domains of the human von Willebrand factor (HsvWF)42. Intramolecular disulfide bridges are shown as yellow sticks and cysteines involved in intermolecular disulfide bonds are shown as dark spheres. b Schematic representation of how such domains allow the formation of long concatemers through intermolecular disulfide bonds is also shown. In the vWF such concatemers achieve specific mechanical properties relevant for biological function. Equivalent interactions have been observed for mucins59,82. c CTCK domain of the human hormone chorionic gonadotropin (HsCG)60. This CTCK domain can form stable dimers without stabilizing intermolecular disulfide bonds. Intramolecular disulfide bonds are shown as yellow sticks and regions involved in dimerization shown as yellow stretches. d Experimental structure of the vWD domain and AlphaFold 2 prediction of the CTCK domain from AmVg. No cysteines are available for the formation of intermolecular disulfide bridges as in the case of vWF or mucins. Vg could achieve dimerization through non-covalent interactions between the CTCK domains, as in the case of chorionic gonadotropin (HsCG) CTCK domain (panel c). The PDB IDs of the relevant structures presented are shown in a light purple box.
