Bacterial Membrane Transport: Superfamilies of Transport Proteins

Abstract

Abstract The bacterial transport systems enable bacteria to accumulate needed nutrients, extrude unwanted by products and maintain cytoplasmic content of protons and salts conducive to growth and development. Two most widely spread superfamilies of transporters are the ion‐coupled systems that take part in chemiosmotic circuits, and the ABC solute ATPases ( adenosine triphosphatases ), whose operation is linked to ATP hydrolysis. The crystal structure of several bacterial transporters has recently been determined, a major breakthrough in the research of transporters. It opened the field to a combined study of structure, function and computation. Several of the structurally deciphered bacterial transporters have eukaryotic orthologues including neurotransmitter transporters that play major roles in health and disease and are major drug targets. Hence, the bacterial transport systems are important both for elucidating the mechanism of transport as well as drug design. Key concepts: Crystal structures are essential for understanding the mechanism of transport. Topology model of transporters obtained from the primary amino acid sequence, the positive‐inside rule and experimental data have been validated by the crystal structure. Primary transporters utilize external source of energy to drive active transport. The secondary transporters utilize the energy stored in a pre‐existing gradient to drive transport. The MFS, major facilitator superfamily, encompasses the largest number of evolutionary related most diverse group of secondary transporters and the extensively studied LacY and GlpT with their crystal structures are educative examples. Na + /H + antiporters are essential for sodium and pH homeostasis in all cells and the most studied Escherichia coli NhaA with its crystal structure is an educative example. The sodium‐coupled secondary transporter LeuT is a bacterial homologue of human neurotransmitters transporters and therefore its crystal structure is an essential step in drug design. The alternating access model is the mechanism of activity of secondary transporters. The molecules of many secondary transporters exhibit internal symmetry that implies a unique evolution. The internal symmetry of secondary transporters with the inverted repeats and the interrupted helices in the middle of the membrane is the structural basis of the activity mechanism.