ABC transporter architecture and regulatory roles of accessory domains

Abstract

We present an overview of the architecture of ATPbinding cassette (ABC) transporters and dissect the systems in core and accessory domains. The ABC transporter core is formed by the transmembrane domains (TMDs) and the nucleotide binding domains (NBDs) that constitute the actual translocator. The accessory domains include the substrate-binding proteins, that function as high affinity receptors in ABC type uptake systems, and regulatory or catalytic domains that can be fused to either the TMDs or NBDs. The regulatory domains add unique functions to the transporters allowing the systems to act as channel conductance regulators, osmosensors/regulators, and assemble into macromolecular complexes with specific properties.

Cystathionine β-Synthase (CBS) Domains 1 and 2 Fulfill Different Roles in Ionic Strength Sensing of the ATP-binding Cassette (ABC) Transporter OpuA

“…methionine in MetD and molybdate or tungstate in ModC) traps the system in the open conformation and thereby provides a negative feedback to the transporter (67,68). Although the CBS domains are structurally unrelated to these accessory domains, the regulatory mechanism has similar consequences (21). Thus, salt-dependent conformational changes in CBS2 are likely to affect the NBD structure (i.e.…”

“…1, A and B) as follows: OpuABC with the substrate-binding domain fused C-terminal to the transmembrane domain (TMD), and OpuAA with tandem CBS domains fused C-terminal to the nucleotidebinding domain (NBD) (21). The active OpuA complex consists of two OpuABC subunits and two OpuAA subunits.…”

Substrate binding by a bacterial ABC transporter involved in polysaccharide export

“…These include domains that are extracytoplasmic or membrane-embedded, as well as regulatory and catalytic domains in the cytoplasm (18). The cytoplasmic regulatory domain of MalK is located C-terminal to the NBD and interacts with the transcriptional regulator MalT (19) as well as with enzyme IIA Glc to effect inducer exclusion (20).…”

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

“…Although ABC transport systems are found in all forms of cellular life, importers are only found in bacteria and archaea and these are dependent on an SBP to provide high affinity substrate binding and delivery to the cognate membrane permease components [58,59]. Thus, SBPs are vital to the specificity and directionality of ABC import systems.…”