Faculty Opinions recommendation of Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing.

2017 ◽  
Author(s):  
Malini Raghavan ◽  
Jie Geng
Keyword(s):  
Mhc I ◽  
Peptide Loading

scholarly journals Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex

2012 ◽  
Vol 69 (19) ◽  
pp. 3317-3327 ◽  
Author(s):  
Sabine Hulpke ◽  
Maiko Tomioka ◽  
Elisabeth Kremmer ◽  
Kazumitsu Ueda ◽  
Rupert Abele ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Mhc I ◽  
Peptide Loading

scholarly journals Atomistic structure and dynamics of the human MHC-I peptide-loading complex

2020 ◽  
Vol 117 (34) ◽  
pp. 20597-20606 ◽  
Author(s):  
Olivier Fisette ◽  
Gunnar F. Schröder ◽  
Lars V. Schäfer
Keyword(s):  
Conformational Dynamics ◽  
Water Environment ◽  
Adaptive Immune System ◽  
Md Simulations ◽  
Class I Mhc ◽  
Mhc I ◽  
Active Core ◽  
Peptide Loading ◽  
Catalytically Active ◽  
Binding Groove

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.

The transporter associated with antigen processing: a key player in adaptive immunity

2015 ◽  
Vol 396 (9-10) ◽  
pp. 1059-1072 ◽  
Author(s):  
Sabine Eggensperger ◽  
Robert Tampé
Keyword(s):  
Adaptive Immunity ◽  
Antigen Processing ◽  
Viral Infections ◽  
Cytotoxic T Cells ◽  
Adaptive Immune System ◽  
Molecular Transport ◽  
Antigenic Peptides ◽  
Mhc I ◽  
Peptide Loading ◽  
Primary Focus

Abstract The adaptive immune system co-evolved with sophisticated pathways of antigen processing for efficient clearance of viral infections and malignant transformation. Antigenic peptides are primarily generated by proteasomal degradation and translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). In the ER, peptides are loaded onto major histocompatibility complex I (MHC I) molecules orchestrated by a multisubunit peptide-loading complex (PLC). Peptide-MHC I complexes are targeted to the cell surface for antigen presentation to cytotoxic T cells, which eventually leads to the elimination of virally infected or malignantly transformed cells. Here, we review MHC I mediated antigen processing with a primary focus on the function and structural organization of the heterodimeric ATP-binding cassette (ABC) transporter TAP1/2. We discuss recent data on the molecular transport mechanism of the antigen translocation complex with respect to structural and biochemical information of other ABC exporters. We further summarize how TAP provides a scaffold for the assembly of the macromolecular PLC, thereby coupling peptide translocation with MHC I loading. TAP inhibition by distinct viral evasins highlights the important role of TAP in adaptive immunity.

scholarly journals Association of TAP Gene Polymorphisms and Risk of Cervical Intraepithelial Neoplasia

2013 ◽  
Vol 35 ◽  
pp. 79-84 ◽  
Author(s):  
Camilla Natter ◽  
Stephan Polterauer ◽  
Jasmin Rahhal-Schupp ◽  
Dan Cacsire Castillo-Tong ◽  
Sophie Pils ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Antigen Processing ◽  
Haplotype Analysis ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Genotype Distribution ◽  
Mhc I ◽  
Haplotype Combination ◽  
Significant Difference ◽  
Peptide Loading

Background.Transporter associated with antigen processing (TAP) is responsible for peptide loading onto class I major histocompatibility complex (MHC-I) molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and contributes to successful eradication of HPV. TAP polymorphisms could have an important impact on the course of HPV infection.Objective.The aim of this study is to evaluate the association between five TAP gene polymorphisms and the risk of CIN.Methods.This case-control study investigated five common TAP polymorphisms in TAP1 (1341 and 2254) and TAP2 (1135, 1693, and 1993) in 616 women with CIN and 206 controls. Associations between gene polymorphisms and risk of CIN were analysed by univariate and multivariable models. The combined effect of the five TAP gene polymorphisms on the risk for CIN was investigated by haplotype analysis.Results.No significant difference in genotype distribution of the five TAP polymorphisms was observed in women with CIN and controls. Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP polymorphisms t1135-t1341-t1693-t1993-t2254) had a significantly lower risk for CIN, compared to women with the haplotype wt-wt-wt-wt-wt (; OR 0.5 []).Conclusion.Identification of this haplotype combination could be used to identify women, less susceptible for development of CIN following HPV infection.

The peptide-loading complex – antigen translocation and MHC class I loading

2009 ◽  
Vol 390 (8) ◽  
Author(s):  
Christian Schölz ◽  
Robert Tampé
Keyword(s):  
Mhc Class I ◽  
Antigen Processing ◽  
Surface Display ◽  
Class I ◽  
Antigenic Peptides ◽  
Mhc I ◽  
Protein Fragments ◽  
Long Term Stability ◽  
Peptide Loading ◽  
Mhc Class I Molecules

Abstract A large and dynamic membrane-associated machinery orchestrates the translocation of antigenic peptides into the endoplasmic reticulum (ER) lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. The peptide-loading complex ensures that only high-affinity peptides, which guarantee long-term stability of MHC I complexes, are presented to T-lymphocytes. Adaptive immunity is dependent on surface display of the cellular proteome in the form of protein fragments, thus allowing efficient recognition of infected or malignant transformed cells. In this review, we summarize recent findings of antigen translocation by the transporter associated with antigen processing and loading of MHC class I molecules in the ER, focusing on the mechanisms involved in this process.

Sign in / Sign up

Export Citation Format

Share Document