Fungal Abc Proteins

The baker’s yeast Saccharomyces cerevisiae was the first eukaryotic organism to have its complete genome sequence determined, revealing 30 distinct genes encoding ATP-binding cassette (ABC) proteins (Bauer et al., 1999; Decottignies and Goffeau, 1997; Taglicht and Michaelis, 1998). ABC proteins are ubiquitous and form one of the largest gene families known with more than 2000 distinct ABC genes present in various current databases, e.g. Interpro (www.ebi.ac.at/interpro/) or Prosite (www.expasy.ch/Prosite). All known ABC proteins share a common hallmark domain, the highly conserved ABC domain, also known as the nucleotide-binding domain (NBD). The NBD contains signature motifs found in all ABC proteins operating from bacteria to man (Higgins, 1992). Membrane-bound ABC proteins also contain variable numbers of membrane-spanning domains arranged in certain membrane architectures. Many ABC proteins transport a variety of compounds across cellular membranes by an active process that is coupled to ATP hydrolysis. These ABC proteins are therefore referred to as ABC transporters or pumps. While some pumps seem to transport various xenobiotics, others exhibit a rather narrow substrate spectrum. Notably, for many ABC proteins no defined substrates or even physiological roles are known. Interestingly, ABC proteins not only function as simple membrane translocators for molecules, they can also act as receptors, sensors, proteases, channels, channel regulators and even signal-ing components (Higgins, 1995). The question of how the highly conserved molecular architecture of ABC proteins entertains such a functional diversity remains elusive. Hence, the functions of many ABC proteins may hold surprises and many important issues remain to be discovered. In this chapter, we will discuss the structure, function and properties of fungal ABC proteins, focusing on the inventory of ABC genes in S. cerevisiae. Because the functional annotation of the yeast genome is fairly advanced, we will also compare the yeast ABC inventory to those from fungal pathogens (Candida albicans and Aspergillus fumigatus) whose genomes have been sequenced or are close to being sequenced.