Project members

PD Dr. Rupert Abele       
Group Leader  
phone +49-(0)69-798-29437

Dr. Christoph Thomas
Postdoctoral Fellow
phone +49-(0)69-798-29486

Dr. Simon Trowitzsch
Group Leader
phone +49-(0)69-798-29273

Susanne Hank
PhD Student
phone: +49-(0)-69-798-29505

Valentina Herbring
PhD Student
phone: +49-(0)-69-798-29505

Sunesh Sethumadhavan
PhD Student
phone: +49-(0)-69-798-29502

Erich Stefan
PhD Student
phone: +49-(0)-69-798-29474

Structure and Mechanism of TAP – Learning from the Expert in Peptide Export

The ABC transporter associated with antigen processing (TAP) shuttles cytosolic peptides into the endoplasmic reticulum (ER). Those antigenic peptides are then loaded onto major histocompatibility complex (MHC) class I molecules for presentation on the cell surface. As the exported antigens reflect viral infections and cellular aberrations, TAP plays a key role in the adaptive immune system.

Unlike the majority of structurally solved ATP-binding cassette (ABC) transporters, the heterodimeric TAP harbors a non-canonical, low-active ATP-binding cassette in one of its half-transporters. The benefit of this functional asymmetry, which is found in many human ABC transporters, remains largely elusive. Given the selectivity of TAP towards short peptides with defined anchor residues, structural and functional studies on TAP provide intriguing insights into both the transport mechanism of an ABC transporter and the relation to its substrate.

In order to decipher the ATPase and peptide transport cycle of TAP, our project group employs biophysical methods such as NMR and EPR, conducts cutting-edge biochemical studies with TAP reconstituted in nanodiscs and proteoliposomes, and expresses TAP and homologous proteins in quantitative amounts for crystallization.

Publications:

Lehnert E, Tampé R.
Structure and Dynamics of Antigenic Peptides in Complex with TAP
Front. Immunol., 30 January 2017 https://doi.org/10.3389/fimmu.2017.00010  PDF

Nöll A, Thomas C, Herbring V, Zollmann T, Barth K, Mehdipour AR, Tomasiak TM, Brüchert S, Joseph B, Abele R, Oliéric V, Wang M, Diederichs K, Hummer G, Stroud RM, Pos KM, Tampé R.
Crystal structure and mechanistic basis of a functional homolog of the antigen transporter TAP.
Proc Natl Acad Sci U S A. 2017 Jan 9. pii: 201620009. doi: 10.1073/pnas.1620009114. [Epub ahead of print]  PDF

Lehnert E, Mao J, Mehdipour AR, Hummer G, Abele R, Glaubitz C, Tampé R.
Antigenic peptide recognition on the human ABC transporter TAP resolved by DNP-enhanced solid-state NMR spectroscopy.
J Am Chem Soc. 2016 Sep 23. [Epub ahead of print] PDF

Fischbach H, Döring M, Nikles D, Lehnert E, Baldauf C, Kalinke U, Tampé R.
Ultrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets.
Nat Commun. 2015 Feb 6;6:6199. doi: 10.1038/ncomms7199. PDF

Kim J, Wu S, Tomasiak TM, Mergel C, Winter MB, Stiller SB, Robles-Colmanares Y, Stroud RM, Tampé R, Craik CS, Cheng Y.
Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter.
Nature. 2014 Nov 2. doi: 10.1038/nature13872. [Epub ahead of print]   PDF

Grossmann N, Vakkasoglu AS, Hulpke S, Abele R, Gaudet R, Tampé R.
Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter.
Nat Commun. 2014 Nov 7;5:5419. doi: 10.1038/ncomms6419.   PDF