News Archive
Mechanistic basis for antigen translocation
November 2014. Life depends on transport systems that move ions and molecules across cell membranes. ATP-binding cassette (ABC) transporters, the largest family of primary active transporters, convert the energy of ATP binding and hydrolysis via two nucleotide-binding domains (NBDs) into conformational changes of two transmembrane domains and thus move a wide range of essential as well as harmful substrates across membranes.
The ABC transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. An international team of scientists headed by Robert Tampé from the Goethe University Frankfurt and Rachelle Gaudet from Harvard University now worked out the mechanistic basis for antigen translocation.
The scientists found that TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. They reveal the importance of the D-loop at the dimer interface of the two NBDs in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the conserved aspartate, which coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. Their data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.
Contact:
Robert Tampé
Goethe-University Frankfurt
Campus Riedberg
Tel.: +49 (0)69 798-29475
tampe@em.uni-frankfurt.de
Full publication:
Grossmann N, Vakkasoglu AS, Hulpke S, Abele R, Gaudet R, Tampé R (2014) Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter. Nat Commun 5:article 5419. Link to full paper