%0 Journal Article
%A Fisette, Olivier
%A Schröder, Gunnar F.
%A Schäfer, Lars V.
%T Atomistic structure and dynamics of the human MHC-I peptide-loading complex
%J Proceedings of the National Academy of Sciences of the United States of America
%V 117
%N 34
%@ 1091-6490
%C Washington, DC
%I National Acad. of Sciences
%M FZJ-2021-00347
%P 20597 - 20606
%D 2020
%X The major histocompatibility complex class-I (MHC-I) peptide-loading complex (PLC) is a cornerstone of the human adaptive immune system, being responsible for processing antigens that allow killer T cells to distinguish between healthy and compromised cells. Based on a recent low-resolution cryo-electron microscopy (cryo-EM) structure of this large membrane-bound protein complex, we report an atomistic model of the PLC and study its conformational dynamics on the multimicrosecond time scale using all-atom molecular dynamics (MD) simulations in an explicit lipid bilayer and water environment (1.6 million atoms in total). The PLC has a layered structure, with two editing modules forming a flexible protein belt surrounding a stable, catalytically active core. Tapasin plays a central role in the PLC, stabilizing the MHC-I binding groove in a conformation reminiscent of antigen-loaded MHC-I. The MHC-I–linked glycan steers a tapasin loop involved in peptide editing toward the binding groove. Tapasin conformational dynamics are also affected by calreticulin through a conformational selection mechanism that facilitates MHC-I recruitment into the complex.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 32788370
%U <Go to ISI:>//WOS:000572978200009
%R 10.1073/pnas.2004445117
%U https://juser.fz-juelich.de/record/889726