Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36115831.
- Also identified by DOI 10.1038/s41467-022-33153-8 and PMC identifier 9482634.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Loading of MHC-I molecules with peptide by the catalytic chaperone tapasin in the peptide loading complex plays a critical role in antigen presentation and immune recognition. Mechanistic insight has been hampered by the lack of detailed structural information concerning tapasin-MHC-I. We present here crystal structures of human tapasin complexed with the MHC-I molecule HLA-B*44:05, and with each of two anti-tapasin antibodies. The tapasin-stabilized peptide-receptive state of HLA-B*44:05 is characterized by distortion of the peptide binding groove and destabilization of the β<sub>2</sub>-microglobulin interaction, leading to release of peptide. Movements of the membrane proximal Ig-like domains of tapasin, HLA-B*44:05, and β<sub>2</sub>-microglobulin accompany the transition to a peptide-receptive state. Together this ensemble of crystal structures provides insights into a distinct mechanism of tapasin-mediated peptide exchange.
Medical subject headings
- Antigen Presentation
- Histocompatibility Antigens Class I