| 總結: | <p>The complement system is a major mechanism of the innate immune system, providing a first line of defence against infection. Many pathogens have evolved mechanisms of evading the complement response by recruitment of complement components onto their surface. Presented here is characterisation of the interface between a complement regulator, factor H, and a protein from <em>Neisseria meningitidis</em>, factor H binding protein (fHbp), which increases complement evasion by the meningococcus. The affinity of the interaction has been measured and experiments have been performed showing that fHbp mimics the glycosaminoglycans found on the surface of host cells. The atomic resolution structure of a mutant form of fHbp that ablates factor H binding is also presented which is a potential vaccine candidate.</p>
<p><em>Borrelia burgdorferi</em> evades complement by recruitment of factor H mediated by the complement regulator acquiring surface protein (CRASP) family of proteins. Investigations into a member of this family, CspA, has revealed that a dimeric form of the protein binds the complement regulator in a high-affinity interaction that utilises a binding site that has been mapped to domains five to seven of factor H. The atomic resolution structure of another member of the CRASP family, ErpC, has been determined that displays a different architecture to fHbp and CspA, yet experiments show that it is capable of binding factor H domains five through seven with an identical affinity. It is hypothesised that the multiple members of the CRASP family enable complement evasion across the range of reservoir hosts and throughout the different stages of the life-cycle of the zoonotic bacterium.</p>
<p>Complement requires tight regulation on order to prevent damage to host cells. The structure of the oligomerisation domains from a complement regulator, C4bp, and a homologue from <em>Gallus gallus</em>, are presented providing the first examples of homoheptameric coiled-coil formation found in nature. Rationalisation of the different C4bp isoforms has also been achieved suggesting that only 7α0β and 7α1β species exist. A new model for incorporation of the beta chain is presented.</p>
<p>The function of the complement factor H related (CFHR) family of proteins has never been reliably elucidated. Presented here is the structure of the N-terminus of CFHR-1 and data showing that CFHR-1, CFHR-2 and CFHR-5 form homo and heterodimeric species which behave as competitive antagonists towards factor H. This results in deregulation of complement, increasing the levels of activation and helping to maintain the homeostatic balance of complement regulation on the surface of host-cells. Rationalisation of the links between complement related diseases and polymorphisms within the CFHR family of proteins is also provided.</p>
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