Principal Investigator
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P9 Rupert Abele
PD, Group Leader
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Institute of Biochemistry
Biocenter
Goethe-University Frankfurt a.M.
Max-von-Laue-Str. 9
60438 Frankfurt am Main, Germany
Phone +49 (0)69 798-29437
Fax +49 (0)69 798-29495
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P9 Function, mechanism and dynamics of the lysosomal transport complex ABCB9
The recently discovered ATP-binding-cassette (ABC) transporter ABCB9 was identified as the peptide transporter which translocates cytosolic peptides into the lumen of the lysosomes. ABCB9 is a member of the ATP-binding-cassette (ABC) tranporter family whose members translocate a broad variety of different solutes under consumption of ATP. ABCB9 forms a homodimer where the so-called half-size transporter is composed of an N-terminal transmembrane domain and a C-terminal nucleotide binding domain. With the help of randomized peptide libraries and reconstituted ABCB9 the peptide specificity concerning the length and the position was deciphered in detail. ABCB9 shows a broad peptide length specificity whereas the N-terminal and the C-terminal residues display the anchor positions. The expression of ABCB9 is strongly upregulated during the differentiation of monocytes to dendritic cells implying its function in antigen processing. However, this peptide transporter is not involved in the classical MHC class I mediated antigen presentation.
In future, we will study the physiological functions of ABCB9 by immunological and cell biological methods. The molecular mechanism and structure of this peptide transporter will be analyzed by biochemical and biophysical approaches, mostly residing in SFB 807.
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Publications
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Bangert, I., Tumulka, F. and Abele, R. (2011) The lysosomal polypeptide transporter TAPL: more than a housekeeping factor? Biol Chem 392, 61-66.
Herget, M., Baldauf, C., Scholz, C., Parcej, D., Wiesmuller, K.H., Tampe, R., Abele, R. and Bordignon, E. (2011) Conformation of peptides bound to the transporter associated with antigen processing (TAP). Proc Natl Acad Sci U S A 108, 1349-1354.
Demirel, Ö., Bangert, I., Tampé, R. and Abele, R. (2010) Tuning the cellular trafficking of the lysosomal peptide transporter TAPL by its N-terminal domain. Traffic 11, 383-393.
Abele, R. and Tampé, R. (2009) Peptide trafficking and translocation across membranes in cellular signaling and self-defense strategies. Curr Opin Cell Biol 21, 508-515.
Herget, M., Kreissig, N., Kolbe, C., Scholz, C., Tampé, R. and Abele, R. (2009) Purification and reconstitution of the antigen transport complex TAP: a prerequisite for determination of peptide stoichiometry and ATP hydrolysis. J Biol Chem 284, 33740-33749.
Zhao, C., Haase, W., Tampé, R. and Abele, R. (2008) Peptide specificity and lipid activation of the lysosomal transport complex ABCB9 (TAPL). J Biol Chem 283, 17083-17091.
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Collaborations
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Prisner (P7), Glaubitz (P6), Kühlbrandt (P1), Michel (P3), Gottschalk (P11)