Molecular Architecture of the TAP-Associated MHC Class I Peptide-Loading Complex
Open Access
- 1 November 2007
- journal article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 179 (9) , 5717-5727
- https://doi.org/10.4049/jimmunol.179.9.5717
Abstract
Tapasin organizes the peptide-loading complex (PLC) by recruiting peptide-receptive MHC class I (MHC-I) and accessory chaperones to the N-terminal regions of the TAP subunits TAP1 and TAP2. Despite numerous studies have shown that the formation of the PLC is essential to facilitate proper MHC-I loading, the molecular architecture of this complex is still highly controversial. We studied the stoichiometry of the PLC by blue native-PAGE in combination with Ab-shift assays and found that TAP/tapasin complexes exist at steady state as a mixture of two distinct oligomers of 350 and 450 kDa. Only the higher m.w. complex contains MHC-I and disulfide-linked tapasin/ER60 conjugates. Moreover, we show for the first time to our knowledge that the fully assembled PLC comprises two tapasin, two ER60, but only one complex of MHC-I and calreticulin. Based hereon we postulate that the TAP subunits alternate in the recruitment and loading of a single MHC-I.Keywords
This publication has 44 references indexed in Scilit:
- Multiple Residues in the Transmembrane Helix and Connecting Peptide of Mouse Tapasin Stabilize the Transporter Associated with the Antigen-processing TAP2 SubunitJournal of Biological Chemistry, 2007
- The first N‐terminal transmembrane helix of each subunit of the antigenic peptide transporter TAP is essential for independent tapasin bindingFEBS Letters, 2006
- The optimization of peptide cargo bound to MHC class I molecules by the peptide‐loading complexImmunological Reviews, 2005
- Mitochondrial Presequence Translocase: Switching between TOM Tethering and Motor Recruitment Involves Tim21 and Tim17Cell, 2005
- Assembly and Antigen-Presenting Function of MHC Class I Molecules in Cells Lacking the ER Chaperone CalreticulinImmunity, 2002
- Thylakoid ΔpH-dependent precursor proteins bind to a cpTatC–Hcf106 complex before Tha4-dependent transportThe Journal of cell biology, 2001
- CELLULAR RESPONSES TO INTERFERON-γAnnual Review of Immunology, 1997
- Roles for Calreticulin and a Novel Glycoprotein, Tapasin, in the Interaction of MHC Class I Molecules with TAPImmunity, 1996
- Functional expression and purification of the ABC transporter complex associated with antigen processing (TAP) in insect cellsFEBS Letters, 1994
- Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigensHuman Immunology, 1984