Tripartite transporters as mechanotransmitters in periplasmic alternating‐access mechanisms

Abstract

To remove xenobiotics from the periplasmic space, Gram-negative bacteria utilise unique tripartite efflux systems in which a molecular engine in the plasma membrane connects to periplasmic and outer membrane subunits. Substrates bind to periplasmic sections of the engine or sometimes to the periplasmic subunits. Then, the tripartite machines undergo conformational changes that allow the movement of the substrates down the substrate translocation pathway to the outside of the cell. The transmembrane (TM) domains of the tripartite resistance-nodulation-drug-resistance (RND) transporters drive these conformational changes by converting proton motive force into mechanical motion. Similarly, the TM domains of tripartite ATP-binding cassette (ABC) transporters transmit mechanical movement associated with nucleotide binding and hydrolysis at the nucleotide-binding domains to the relevant subunits in the periplasm. In this way, metabolic energy is coupled to periplasmic alternating-access mechanisms to achieve substrate transport across the outer membrane.

Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria

“…More recently, Murakami et al 580 also extended their DALI analysis to the type V family members ABCG2 (PDB ID 5NJG) 632 and ABCA1 (PDB ID 5XJY) 633 that returned high Z-score values of 7.6 and 7.5, respectively. While the overall score is lower, these transporters allow better superposition, covering all four TMs of MacB, and importantly, they provide a dimer interface matching that of the MacB.…”

“…General Topology of MacB/FtsX Family and TM Domains. The recent determination of a number of MacB/ FtsX family transporter structures 24,272,431,571 has revealed a number of unique features within the TM region of these transporters, and these have been the subject of several excellent reviews (see Greene et al 442 and Murakami et al 580 ).…”

Structural and functional characteristics of the tripartite ABC transporter

“…In conclusion, recent structural and functional analyses of MacB and LolCDE identified unique features of type VII ABC transporters, and introduced a new 'mechanotransmitter' concept to the ABC transporter superfamily. Several models of substrate translocation by the tripartite ABC transporter were proposed, such as the 'fireplace bellows mechanism, ' the 'periplasmic alternating-access mechanism, ' or the 'modified bellow model' [44,46,47]. Structural analyses of the substrate-bound states of type VII ABC transporters such as LolCDE or HrtBA revealed the molecular mechanisms of the substrate recognition [36,41,42].…”

The incredible diversity of structures and functions of ABC transporters

“…Additionally, advances in single molecule techniques and theoretical approaches show great potential to help investigate these aspects of ABC transporter mechanisms [8–12]. A major conclusion is that structural information should always be interpreted taking into consideration all available biochemical and genetic studies, as well as the technical limitations of in vitro membrane‐mimicking environments, as opposed to the native membrane of a living cell [13–17].…”