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Title: Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [1];  [1];  [3];  [4];  [4];  [5];  [5];  [2];  [1];  [1]
  1. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases. Lab. of Immunology. Molecular Biology Section
  2. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Biomedical Imaging and Bioengineering. Lab. of Cellular Imaging and Macromolecular Biophysics
  3. National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases. Office of Cyber Infrastructure and Computational Biology. Bioinformatics and Computational Biosciences Branch
  4. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research. Lab. of Immunology
  5. Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States). Dept. of Microbiology and Immunology
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Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8+ T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC-I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC-I, permitting peptide editing.

Research Organization:
National Institutes of Health (NIH), Bethesda, MD (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)
Contributing Organization:
Food and Drug Administration (FDA), Silver Spring, MD (United States); Univ. of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)
Grant/Contract Number:
AC02-06CH11357; 9 P41 GM103622; AI0000394; EB000008; 1617
OSTI ID:
1242290
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 8; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 62 works
Citation information provided by
Web of Science

References (44)

TAPBPR: a new player in the MHC class I presentation pathway: TAPBPR in MHC class I antigen presentation journal February 2015
Design and use of conditional MHC class I ligands journal February 2006
The ABCs of Immunology: Structure and Function of TAP, the Transporter Associated with Antigen Processing journal August 2004
DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering journal January 2009
Excess β2 microglobulin promoting functional peptide association with purified soluble class I MHC molecules journal January 1991
CRYSOL – a Program to Evaluate X-ray Solution Scattering of Biological Macromolecules from Atomic Coordinates journal December 1995
The Binding of TAPBPR and Tapasin to MHC Class I Is Mutually Exclusive journal October 2013
PRIMUS: a Windows PC-based system for small-angle scattering data analysis journal September 2003
Running the gauntlet: from peptide generation to antigen presentation by MHC class I journal July 2011
Rethinking peptide supply to MHC class I molecules journal May 2007
Major Histocompatibility Complex Class I-ERp57-Tapasin Interactions within the Peptide-loading Complex journal April 2007
SEDPHAT – A platform for global ITC analysis and global multi-method analysis of molecular interactions journal April 2015
Overview of Current Methods in Sedimentation Velocity and Sedimentation Equilibrium Analytical Ultracentrifugation journal February 2013
TAPBPR isoforms exhibit altered association with MHC class I journal April 2014
Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling journal March 2000
Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway journal February 2013
Structural characterization of a soluble and partially folded class I major histocompatibility heavy chain/β2m heterodimer journal May 1998
The glucose transporter of Escherichia coli : Purification and characterization by Ni journal June 1993
In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides journal November 2006
Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter journal May 1991
HLA-A2-peptide complexes: refolding and crystallization of molecules expressed in Escherichia coli and complexed with single antigenic peptides. journal April 1992
Characterization and use of the Drosophila metallothionein promoter in cultured Drosophila melanogaster cells journal January 1988
Critical factors in the development of fluorescence polarization-based peptide binding assays: An equilibrium study monitoring specific peptide binding to soluble HLA-A⁎0201 journal July 2006
Association of ERp57 with Mouse MHC Class I Molecules Is Tapasin Dependent and Mimics That of Calreticulin and not Calnexin journal June 2001
Recruitment of MHC Class I Molecules by Tapasin into the Transporter Associated with Antigen Processing-Associated Complex Is Essential for Optimal Peptide Loading journal February 2002
A humanTAPBP (TAPASIN)-related gene,TAPBP-R journal April 2002
Multiple mapping method: A novel approach to the sequence-to-structure alignment problem in comparative protein structure modeling journal January 2006
Monitoring peptide processing for MHC class I molecules in the endoplasmic reticulum journal February 2014
Restoring Low Resolution Structure of Biological Macromolecules from Solution Scattering Using Simulated Annealing journal June 1999
Pathways of Antigen Processing journal March 2013
A Point Mutation in HLA-A*0201 Results in Failure to Bind the TAP Complex and to Present Virus-Derived Peptides to CTL journal May 1996
MHC class I antigen presentation: learning from viral evasion strategies journal July 2009
Chaperones and folding of MHC class I molecules in the endoplasmic reticulum journal June 2003
Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer journal July 2007
HLA-A*0201 presents TAP-dependent peptide epitopes to cytotoxic T lymphocytes in the absence of tapasin journal October 1998
Measuring Protein‐Protein Interactions by Equilibrium Sedimentation journal November 2007
ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum journal October 2002
ERAAP and Tapasin Independently Edit the Amino and Carboxyl Termini of MHC Class I Peptides journal July 2013
The Biochemistry and Cell Biology of Antigen Processing and Presentation journal April 1993
The role of mRNA translation in direct MHC class I antigen presentation journal February 2012
Insights into MHC Class I Peptide Loading from the Structure of the Tapasin-ERp57 Thiol Oxidoreductase Heterodimer journal January 2009
Roles for Calreticulin and a Novel Glycoprotein, Tapasin, in the Interaction of MHC Class I Molecules with TAP journal August 1996
Recurrent turnover of senescent cells during regeneration of a complex structure journal May 2015
TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst journal October 2015

Cited By (21)

TAPBPR mediates peptide dissociation from MHC class I using a leucine lever journal November 2018
A personal retrospective on the mechanisms of antigen processing journal January 2019
TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway text January 2017
Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle journal July 2018
Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation journal October 2017
Structure of the TAPBPR–MHC I complex defines the mechanism of peptide loading and editing journal October 2017
The Role of Molecular Flexibility in Antigen Presentation and T Cell Receptor-Mediated Signaling journal July 2018
TAPBPR mediates peptide dissociation from MHC class I using a leucine lever posted_content November 2018
High Throughput pMHC-I Tetramer Library Production Using Chaperone Mediated Peptide Exchange posted_content November 2019
TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway journal April 2017
Structural aspects of chaperone-mediated peptide loading in the MHC-I antigen presentation pathway journal March 2019
Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection posted_content September 2019
MHC Molecules, T cell Receptors, Natural Killer Cell Receptors, and Viral Immunoevasins—Key Elements of Adaptive and Innate Immunity book October 2019
Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules journal September 2018
TAPBPR mediates peptide dissociation from MHC class I using a leucine lever. text January 2018
Whole genome duplications have provided teleosts with many roads to peptide loaded MHC class I molecules journal February 2018
Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection journal December 2019
Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules. text January 2018
Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control journal January 2017
Preferential interaction of MHC class I with TAPBPR in the absence of glycosylation. journalarticle January 2019
Proofreading of Peptide—MHC Complexes through Dynamic Multivalent Interactions journal February 2017

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Related Subjects

60 APPLIED LIFE SCIENCES
antigen presentation
peptide loading
major histocompatibility complex
protein interactions
SAXS