Title: | Direct peptide-regulatable interactions between MHC class I molecules and tapasin |
Address: | "Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA" |
ISSN/ISBN: | 0027-8424 (Print) 1091-6490 (Electronic) 0027-8424 (Linking) |
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" |
Keywords: | Animals CHO Cells Cricetinae Histocompatibility Antigens Class I/isolation & purification/*metabolism Membrane Transport Proteins/genetics/*metabolism Peptides/*metabolism Protein Binding Temperature beta 2-Microglobulin/metabolism; |
Notes: | "MedlineRizvi, Syed Monem Raghavan, Malini eng R01 AI044115/AI/NIAID NIH HHS/ R56 AI044115/AI/NIAID NIH HHS/ AI-44115/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2006/11/23 Proc Natl Acad Sci U S A. 2006 Nov 28; 103(48):18220-5. doi: 10.1073/pnas.0605131103. Epub 2006 Nov 20" |