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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rizvi, Syed Monem Raghavan, Malini |
| Description | Author Affiliation: Rizvi SM ( Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.); |
| Abstract | Tapasin (Tpn) has been implicated in multiple steps of the MHC class I assembly pathway, but the mechanisms of function remain incompletely understood. Using purified proteins, we could demonstrate direct binding of Tpn to peptide-deficient forms of MHC class I molecules at physiological temperatures. Tpn also bound to M10.5, a pheromone receptor-associated MHC molecule that has an open and empty groove and that shares significant sequence identity with class I sequences. Two types of MHC class I-Tpn complexes were detectable in vitro depending on the input proteins; those depleted in beta(2)m, and those containing beta(2)m. Both were competent for subsequent assembly with peptides, but the latter complexes assembled more rapidly. Thus, the assembly rate of Tpn-associated class I was determined by the conditions under which Tpn-MHC class I complexes were induced. Peptide loading of class I inhibited Tpn-class I-binding interactions, and peptide-depletion enhanced binding. In combination with beta(2)m, certain peptides induced efficient dissociation of preformed Tpn-class I complexes. Together, these studies demonstrate direct Tpn-MHC class I interactions and preferential binding of empty MHC class I by Tpn, and that the Tpn-class I interaction is regulated by both beta(2)m and peptide. In cells, Tpn is likely to be a direct mediator of peptide-regulated binding and release of MHC class I from the TAP complex. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Histocompatibility Antigens Class I Metabolism Membrane Transport Proteins Peptides Animals CHO Cells Cricetinae Isolation & Purification Genetics Protein Binding Temperature Beta 2-Microglobulin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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