Antigenic Peptide Recognition on the Human ABC Transporter TAP Resolved by DNP-Enhanced Solid-State NMR Spectroscopy

• DOI: 10.1021/jacs.6b07426
• Publication Date: 2016-09-23T12:01:14Z
• Authors: Elisa Lehnert; Jiafei Mao; Ahmad Reza Mehdipour; Gerhard Hummer; Rupert Abele; Clemens Glaubitz; Robert Tampé
• Keywords: Magic angle spinning

The human transporter associated with antigen processing (TAP) is a 150 kDa heterodimeric ABC transport complex that selects peptides for export into the endoplasmic reticulum and subsequent loading onto major histocompatibility class I molecules to trigger adaptive immune responses against virally or malignantly transformed cells. To date, no atomic-resolution information on peptide–TAP interactions has been obtained, hampering mechanistic understanding of early steps substrate translocation catalyzed by TAP. Here, we developed mild method concentrate an unstable membrane protein combined this effort dynamic nuclear polarization enhanced magic angle spinning solid-state NMR study challenging protein–substrate complex. We were able determine backbone conformation antigenic peptide bound Our data also provide unparalleled insights nature between side chains By combining molecular modeling, location binding cavity identified, revealing scenario recognition. findings reveal structural chemical basis selection rules, which define crucial function in immunity health. This work first eukaryotic presents power growing field.