Hypothetical model of the interaction of the HD with HS chains. Due to the large size of the HD, several binding sites could be present within the HD sequence. In this model, only the conserved outer regions contribute to HS binding. In the HDC mutant, two HS binding sites come into close contact, allowing high affinity binding of the shortened HD within one S-domain, whereas in the full-length HD, both binding sites cannot bind within the same S-domain. Thus, tight binding of HD requires “tandem” contacts with two S-domains.