AMINO-ACID TRANSPORTERS OF LOWER EUKARYOTES - REGULATION, STRUCTURE AND TOPOGENESIS

Lower eukaryotes such as the yeast Saccharomyces cerevisiae and the fi lamentous fungus Aspergillus nidulans possess a multiplicity of amino acid transporters or permeases which exhibit different properties with respect to substrate affinity, specificity, capacity and regulation. Regulation of amino acid uptake in response to physiological condition s of growth is achieved principally by a dual mechanism; control of ge ne expression, mediated by a complex interplay of pathway-specific and wide-domain transcription regulatory proteins, and control of transpo rt activities, mediated by a series of protein factors, including a ki nase, and possibly, by amino acids. All fungal and a number of bacteri al amino acid permeases show significant sequence similarities (33-62% identity scores in binary comparisons), revealing a unique transporte r family conserved across the prokaryotic-eukaryotic boundary. Predict ion of the topology of this transporter family utilizing a multiple se quence alignment strongly suggests the presence of a common structural motif consisting of 12 alpha-helical putative transmembrane segments and cytoplasmically located N- and C-terminal hydrophilic regions. Int erestingly, recent genetic and molecular results strongly suggest that yeast amino acid permeases are integrated into the plasma membrane th rough a specific intracellular translocation system. Finally, speculat ing on their predicted structure and on amino acid sequence similariti es conserved within this family of permeases reveals regions of putati ve importance in amino acid transporter structure, function, post-tran slational regulation or biogenesis.