Transport Properties of Cryptosporidium parvum CPABC

Cryptosporidium parvum is an important opportunistic infection in persons with the acquired immunodeficiency syndrome (AIDS). C. parvum is an intracellular parasite that invades epithelial cells in the gastrointestinal tract where it develops inside a vacuole at the apex of the host cell. Intracellular parasites must obtain nutrients from the host cell, and these materials have to cross the membrane(s) of the host-parasite boundary. The transport pathways essential for parasite development are poorly understood in C. parvum. The major host-parasite interface in C. parvum-infected cells is an extensively folded membranous structure known as the feeder organelle. CpABC is a C. parvum ATP-binding cassette (ABC) transporter protein localized to the feeder organelle region. CpABC is the first transporter to be identified in C. parvum, and it is the first protein to be localized to the feeder organelle region. CpABC shares conserved features of protein structure with the multidrug resistance protein (MRF) subfamily of ABC transporter proteins. The structure and location of CpABC suggests that it plays an important role in the regulation of transport in the developing parasite.
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The objective of this proposal is to elucidate the transport properties of CpABC. This will be accomplished through the use of two tractable model systems: the baculovirus-insect cell expression system and the yeast Saccharomyces cerevisiae. The aims are: 1) to characterize CpABC biochemically by the analysis of ATPase and transport activities. 2) to characterize CpABC by functional analyses in yeast. The long term goal is to understand the physiological role of CpABC and the functioning of the feeder organelle.