The ABC proteins family: an amazing machinery. Structure and mechanism of transport.

Abstract

The proper functioning of all living organisms depends on the supply of essential nutrients from the outside and the removal of harmful toxic compounds from the cells by primary and secondary membrane transport. The ABC transporters constitute the largest family of the proteins identified to date. They are ubiquitous among all living organisms, both Eukaryotes and Prokaryotes. In the group of proteins which form so called human transportome, exist 49 ABC transporters. In addition to performing important physiological functions (e.g. detoxification of the organism, being an essential element of blood-brain barrier, maintainance of lipid homeostasis or participation in cellular immune response), they also play a significant role in the pathogenesis of numerous diseases, including cystic fibrosis, Tanger disease and cancer. Primarily, the ABC proteins are responsible for the active export of a wide variety of substrates (including, for example: organic and inorganic ions, proteins, amino acids, oligonucleotides, complex carbohydrates, heavy metals, steroids, bile salts, vitamins, antibiotics, anti-cancer drugs and their metabolites, as well as many important signaling molecules, e.g. cysteinyl leukotrienes and prostaglandins) outside the cell which is driven by the hydrolysis of ATP. The minimal functional unit for efficient transport consists of two nucleotide binding domains (NBDs) and two trans-membrane domains (TMDs). The highly conserved NBD domains form the ATP-dependent driving force for transport. Each NBDs consists of RecA-like and α-helical subdomains which include the following conservative motifs: Walker A motif, Walker B motif, H switch region, A-, Q-, D- loops as well as consensus C sequence. In turn, more structurally diverse TMD domains determine the substrate specificity of ABC proteins and create the translocation pathway across the lipid bilayer. This publication presents various strategies for substance transport and the structural complexity of the ABC transporters.

Keywords

• structure
• abc transporters
• transport mechanism