Details

Autor(en) / Beteiligte

• Margulies, David H
• Jiang, Jiansheng
• Natarajan, Kannan

Titel

Structural and dynamic studies of TAPBPR and Tapasin reveal the mechanism of peptide loading of MHC-I molecules

Ist Teil von

• Current opinion in immunology, 2020-06, Vol.64, p.71-79

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •Peptide/MHC complexes serve for recognition by T and NK cells.•Loading of peptide on MHC-I depends on either the tapasin-containing PLC or on TAPBPR.•Structural studies of tapasin and TAPBPR lead to understanding of mechanism of peptide loading.•Crucial parts of the TAPBPR molecule reveal dynamic motion as observed in X-ray, NMR, and molecular dynamics studies. Major histocompatibility complex encoded class I (MHC-I) molecules bind a broad spectrum of peptides generated in the cytoplasm and encountered during protein folding and maturation in the endoplasmic reticulum (ER). For cell surface expression and recognition by T cell receptors (TCR) and natural killer (NK) receptors, MHC-I require loading with high affinity peptides. Peptide optimization is catalyzed by either of two pathways. The first is via the peptide-loading complex (PLC) which consists of the transporter associated with antigen processing (TAP)1/TAP2 heterodimer, tapasin (an ER resident chaperone, also known as TAP-binding protein (TAPBP)), ERp57 (an oxidoreductase), and calreticulin (a sugar-binding chaperone) [1]. The second pathway depends on TAP-binding protein, related (TAPBPR), a PLC-independent chaperone, that is similar in amino acid sequence and structure to tapasin [2]. Until recently, mechanistic understanding of how the PLC or TAPBPR influences MHC-I peptide loading has been hampered by a lack of detailed structural information on the modification of the MHC-I peptide-binding site by chaperone interactions. Here we review recent functional, structural, and computational dynamic studies of tapasin and TAPBPR that contribute to a vivid description of the molecular changes in MHC-I molecules that accompany tapasin or TAPBPR interaction.