Peptide specificity and lipid activation of the lysosomal transport complex ABCB9 (TAPL)

The Journal of Biological Chemistry
Chenguang ZhaoRupert Abele

Abstract

The lysosomal ABC transporter associated with antigen processing-like (TAPL, ABCB9) acts as an ATP-dependent polypeptide transporter with broad length selectivity. To characterize in detail its substrate specificity, a procedure for functional reconstitution of human TAPL was developed. By intensive screening of detergents, ideal solubilization conditions were evolved with respect to efficiency, long term stability, and functionality of TAPL. TAPL was isolated in a two-step procedure with high purity and, subsequently, reconstituted into proteoliposomes. The peptide transport activity of reconstituted TAPL strongly depends on the lipid composition. With the help of combinatorial peptide libraries, the key positions of the peptides were localized to the N- and C-terminal residues with respect to peptide transport. At both ends, TAPL favors positively charged, aromatic, or hydrophobic residues and disfavors negatively charged residues as well as asparagine and methionine. Besides specific interactions of both terminal residues, electrostatic interactions are important, since peptides with positive net charge are more efficiently transported than negatively charged ones.

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Citations

Apr 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Chenguang ZhaoChristian Schlieker
Jan 5, 2011·Biological Chemistry·Irina BangertRupert Abele
Aug 25, 2009·Trends in Immunology·Rieneke van de VenTanja D de Gruijl
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Sep 17, 2014·Journal of Molecular Biology·Peter U Mayerhofer, Robert Tampé
Feb 27, 2015·Biological Chemistry·Tina ZollmannRupert Abele
May 16, 2018·Frontiers in Cell and Developmental Biology·Rupert Abele, Robert Tampé
Oct 25, 2020·FEBS Letters·Gergely Szakacs, Rupert Abele
Jun 27, 2018·Molecular Immunology·Myriam LawandPeter van Endert
May 30, 2012·Journal of Cell Science·Özlem DemirelRupert Abele
Feb 14, 2019·Chemical Reviews·Valentina CorradiD Peter Tieleman

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