Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation
Year: 2022
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Awards: G2099282922, G2595820228, Molecular mechanism of antigen editing by Class-I MHC Chaperones, G4440517329, G5095058752, G5685496259, G5980951248, G603226791, G6188634283, G6550433311, G7457220623, An integrative structural biology approach to the study of T cell signaling, G759790585, G7960256069, Mechanisms of antigen cross-presentation by MHC class I molecules, G8101592984, G9000053225, Molecular Genetic Analysis Of Lymphocyte Function
OpenAlex ID: W4296139744