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ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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ABC transporters in adaptive immunity.

Fabian Seyffer1, Robert Tampé2

  • 1Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.

Biochimica Et Biophysica Acta
|June 14, 2014
PubMed
Summary

The transporter associated with antigen processing (TAP) uses ATP to move peptides into the endoplasmic reticulum for immune response. Viral factors can block TAP, preventing immune cell detection.

Keywords:
ABC proteinAntigen processingMembrane proteinsTransport ATPasesTransporter associated with antigen processingViral immune escape

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Area of Science:

  • Structural biology and biophysics of membrane proteins.
  • Molecular mechanisms of solute transport.
  • Immunology and host-pathogen interactions.

Background:

  • ATP-binding cassette (ABC) transporters are vital membrane proteins found across all life forms.
  • These transporters utilize ATP hydrolysis to move diverse solutes across cellular membranes.
  • Understanding their conformational changes is key to elucidating transport mechanisms.

Purpose of the Study:

  • To detail the functional modules, ATPase cycle, and transport mechanism of the heterodimeric transporter associated with antigen processing (TAP1/2).
  • To explore the interactions of TAP with other cellular components and its modulation by viral factors.
  • To provide a working model of the TAP transport cycle and its inhibition by viral elements.

Main Methods:

  • Analysis of crystal structures of ABC transport systems to understand conformational states.
  • Functional characterization of TAP1/2, focusing on its ATPase activity and transport cycle.
  • Investigation of viral factor interactions with TAP to understand immune evasion strategies.

Main Results:

  • TAP1/2 functions as a crucial component of the adaptive immune system, transporting peptides into the endoplasmic reticulum for MHC class I presentation.
  • Viral factors were identified to inhibit TAP activity, thereby hindering the detection of infected cells by cytotoxic T-cells.
  • Structural and functional data were integrated to refine the understanding of solute transport by TAP.

Conclusions:

  • TAP serves as an ideal model system for studying ABC transporters due to its defined substrate, viral inhibitors, and role in adaptive immunity.
  • The study delineates a working model for the TAP transport cycle, including how viral factors arrest TAP in specific conformations.
  • Understanding TAP's mechanism provides insights into the broader principles governing human ABC transporter function and regulation.