Get into the groove! The influence of TAPBPR on cargo selection

Satti, Reem; Morley, John E.; Boyle, Louise H.

doi:10.1016/j.coi.2023.102346

Cited by 2 publications

(1 citation statement)

References 37 publications

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“…Beginning with the determination of the structure of the chaperone tapasin bound to another stabilizing component ERp57 (also known as PDIA3) (Dong et al, 2009), several additional structures determined by X-ray crystallography (Jiang et al, 2017;Thomas & Tampe ´, 2017;Mu ¨ller et al, 2022;Jiang et al, 2022) or cryoEM (Blees et al, 2017;Domnick et al, 2022) have augmented a structure-based mechanistic view of chaperone function. Several recent review papers on this topic are primarily based on a biological perspective (Margulies et al, 2022;Margulies, Jiang et al, 2023;Turner et al, 2023;van Hateren & Elliott, 2023;Lan et al, 2023;Satti et al, 2023). This review will emphasize a structural point of view (Table 1) and the principles governing peptide exchange.…”

Section: Introductionmentioning

confidence: 99%

Chaperone-mediated MHC-I peptide exchange in antigen presentation

Jiang,

Natarajan,

Margulies

2024

Int Union Crystallogr J

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This work focuses on molecules that are encoded by the major histocompatibility complex (MHC) and that bind self-, foreign- or tumor-derived peptides and display these at the cell surface for recognition by receptors on T lymphocytes (T cell receptors, TCR) and natural killer (NK) cells. The past few decades have accumulated a vast knowledge base of the structures of MHC molecules and the complexes of MHC/TCR with specificity for many different peptides. In recent years, the structures of MHC-I molecules complexed with chaperones that assist in peptide loading have been revealed by X-ray crystallography and cryogenic electron microscopy. These structures have been further studied using mutagenesis, molecular dynamics and NMR approaches. This review summarizes the current structures and dynamic principles that govern peptide exchange as these relate to the process of antigen presentation.

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Section: Introductionmentioning

confidence: 99%

Chaperone-mediated MHC-I peptide exchange in antigen presentation

Jiang,

Natarajan,

Margulies

2024

Int Union Crystallogr J

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Reanalysis of Immunopeptidomics Datasets Provides Mechanistic Insight into TAPBPR-Mediated Peptide Editing on HLA-A, -B and -C Molecules

Altenburg,

Morley,

Bauer

et al. 2024

Wellcome Open Res

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Background Major histocompatibility class I (MHC-I, human leukocyte antigen [HLA]-I in humans) molecules present small fragments of the proteome on the cell surface for immunosurveillance, which is pivotal to control infected and malignant cells. Immunogenic peptides are generated and selected in the MHC-I antigen processing and presentation pathway. In this pathway, two homologous molecules, tapasin and TAPBPR, optimise the MHC-I peptide repertoire that is ultimately presented at the plasma membrane. Peptide exchange on HLA-I by human TAPBPR involves the flexible loop region K22-D35, with the leucine at position 30 (L30) involved in mediating peptide dissociation. However, our understanding of the exact molecular mechanisms governing TAPBPR-mediated peptide exchange on HLA-I allotypes remains incomplete. Methods Here, in-depth re-analyses of published immunopeptidomics datasets was used to further examine TAPBPR peptide editing activity and mechanism of action on HLA-I. The role of the TAPBPR editing loop in opening the HLA-I peptide binding groove was assessed using a molecular dynamics simulation. Results We show that TAPBPR shapes the peptide repertoire on HLA-A, -B and -C allotypes. The TAPBPR editing loop was not essential to allow HLA-I to adopt an open state. L30 in the TAPBPR editing loop was typically sufficient to mediate peptide repertoire restriction on the three HLA-I allotypes expressed by HeLa cells. TAPBPR was also able to load peptides onto HLA-I in a loop-dependent manner. Conclusions These results unify the previously hypothesised scoop loop and peptide trap mechanisms of TAPBPR-mediated peptide exchange, with the former involved in peptide filtering and the latter in peptide loading.

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Get into the groove! The influence of TAPBPR on cargo selection

Cited by 2 publications

References 37 publications

Chaperone-mediated MHC-I peptide exchange in antigen presentation

Chaperone-mediated MHC-I peptide exchange in antigen presentation

Reanalysis of Immunopeptidomics Datasets Provides Mechanistic Insight into TAPBPR-Mediated Peptide Editing on HLA-A, -B and -C Molecules

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