ABC Transporters in Dynamic Macromolecular Assemblies

J Mol Biol. 2018 Oct 26;430(22):4481-4495. doi: 10.1016/j.jmb.2018.07.028. Epub 2018 Aug 5.

Abstract

ATP-binding cassette (ABC) transporters constitute one of the largest families of integral membrane proteins, including importers, exporters, channels, receptors, and mechanotransducers, which fulfill a plethora of cellular tasks. ABC transporters are involved in nutrient uptake, hormone and xenobiotic secretion, ion and lipid homeostasis, antibiotic and multidrug resistance, and immunity, thus making them prime candidates for cellular regulation and pharmacological intervention. In recent years, numerous various structures of ABC transporters have been determined by X-ray crystallography or cryogenic electron microscopy. Structural and functional studies revealed that various auxiliary domains play key roles for the subcellular localization of ABC transporters and recruitment of regulatory factors. In this regard, the ABC transporter associated with antigen processing TAP stands out. In the endoplasmic reticulum membrane, TAP assembles the peptide-loading complex, which serves as a central checkpoint in adaptive immunity. Here, we discuss the various aspects of auxiliary domains for ABC transporter function with a particular emphasis on the structure of the peptide-loading complex, which is crucial for antigen presentation in adaptive immunity.

Keywords: ER quality control; adaptive immunity; glycosylation; major histocompatibility complex; membrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Homeostasis
  • Humans
  • Lipid Metabolism
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Domains
  • Protein Transport

Substances

  • ATP-Binding Cassette Transporters
  • Multiprotein Complexes