MRC National Institute for Medical Research, London
Science for Health
Mike Blackman group project:
Proteolytic processing and function of apical membrane antigen-1 (AMA1)
AMA1 is a large integral membrane protein that is secreted from micronemes, a set of specialised apically-located secretory organelles, onto the surface of the merozoite just prior to invasion. There AMA1 plays a critical role in invasion and is eventually shed by the action of PfSUB2 (Harris et al., 2005). AMA1 is of particular interest because antibodies against it can prevent host cell invasion by the parasite. We wish to determine the function of AMA1 and the role of its shedding, as well as defining functionally important regions of the protein that might form part of a sub-unit malaria vaccine (Pizarro et al., 2005). To this end, we have mapped the epitope for one of the most efficient monoclonal antibodies which inhibit invasion (Collins et al., 2007). Present research includes identification of binding partners for AMA1.
X-ray crystal structure of the AMA1 ectodomain
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The X-ray crystal structure of the AMA1 ectodomain has shown that it comprises three disulphide-constrained domains. Two of these belong to the PAN module superfamily, implicated in protein-protein or protein-carbohydrate interactions. Here, domains I (yellow), II (blue) and III (green) are shown in three orientations.
Blackman group
Recent publications
Research projects
- Proteolytic processing and function of apical membrane antigen-1 (AMA1)
- Subtilisin-like proteases of the malaria merozoite
- Rhomboid-like proteases in red blood cell invasion
Blackman biography
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