Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation
Abstrak
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 2 -microglobulin interaction, leading to release of peptide. Movements of the membrane proximal Ig-like domains of tapasin, HLA-B*44:05, and β 2 -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.
Penulis (12)
Jiansheng Jiang
Daniel K. Taylor
Ellen J. Kim
Lisa F. Boyd
Javeed Ahmad
Michael G. Mage
Hau V. Truong
Claire H. Woodward
Nikolaos G. Sgourakis
Peter Cresswell
David H. Margulies
Kannan Natarajan
Akses Cepat
- Tahun Terbit
- 2022
- Bahasa
- en
- Total Sitasi
- 47×
- Sumber Database
- CrossRef
- DOI
- 10.1038/s41467-022-33153-8
- Akses
- Open Access ✓