RESEARCH SUMMARY

Some viruses and bacteriophages attach to their host cell via proteins integral to their capsids, for example poliovirus, coxsackievirus and rhinovirus ('common cold virus'). Other viruses bind to their host cell receptors via specialised spike proteins (for example HIV, the AIDS-virus), or via specialised fibre proteins, like adenovirus, reovirus and bacteriophages like T4, T5, T7 and lambda (Ur). These fibres all have the same basic architecture: they are trimeric and contain an N-terminal virus or bacteriophage attachment domain, a long, thin, but stable shaft domain and a more globular C-terminal cell attachment domain. These trimeric, fibrous proteins are very stable to denaturation by temperature or detergents. Our goal is to determine the structures of these proteins and thus to make an extensive inventory of stable trimeric fibrous folds present in nature.

Knowledge of the structures of viral and bacteriophage fibre proteins may lead to different biotechnological applications. As adenovirus is used in experimental gene therapy, modification of its fibre should allow targeting to specific cellular receptors. Modification of the bacteriophage fibre receptor binding specificities may lead to improved detection and elimination of specific bacteria.

We also collaborate with other research groups in crystallisation and structure solutions of the proteins and peptides they produce and have determined structures of avian reovirus proteins, cyclic antibiotic peptides and bacterial dehydroquinases complexed with inhibitors.