MRC National Institute for Medical Research, London
Science for Health
Mike Blackman group project:
Rhomboid-like proteases in red blood cell invasion
Rhomboids are a family of relatively recently-discovered class of serine proteases that have the unusual capacity to cleave substrates within their transmembrane domains. There is growing evidence that rhomboids mediate key proteolytic processing activities during invasion by apicomplexan parasites (Zhou et al., 2004). A number of rhomboid-like proteases are encoded by the P. falciparum genome, and we are examining the function, activity and sub-cellular location of these proteins. We are also actively investigating a family of putative rhomboid substrates on the merozoite surface.
Model for role of rhomboid-like proteases during red blood cell invasion by the malaria merozoite
Click image to view at full-size
The model is based on work in the related apicomplexan parasite Toxoplasma gondii. Initial binding (A) is mediated by surface-resident adhesins such as MSP1 (not shown for clarity). Reorientation and junction formation (B) is through limited release of higher affinity adhesins (blue) from micronemes. Rapid upregulation of microneme secretion then occurs; the adhesins interact with a sub-plasmalemmal actinomyosin motor and are translocated towards the posterior pole of the parasite (C-D), in the process driving forward motion of the parasite. The adhesins finally come into contact with a rhomboid-like protease (green) located at the posterior pole, when they are cleaved within their transmembrane domains and released (E), allowing completion of invasion.
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
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA
Top of page