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1000 Titel
  • Characterization of Structural Features Controlling the Receptiveness of Empty Class II MHC Molecules
1000 Autor/in
  1. Rupp, Bernd |
  2. Makhmoor, Talat |
  3. Dickhaut, Katharina |
  4. Gupta, Shashank |
  5. Choudhary, Iqbal |
  6. Wiesmüller, Karl-Heinz |
  7. Jung, Günther |
  8. Freund, Christian |
  9. Falk, Kirsten |
  10. Rötzschke, Olaf |
  11. Kühne, Ronald |
  12. Schlundt, Andreas |
  13. Günther, Sebastian |
1000 Erscheinungsjahr 2011
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2011-04-14
1000 Erschienen in
1000 Quellenangabe
  • 6(4): e18662
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2011
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.pone.0018662 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077389/ |
1000 Ergänzendes Material
  • http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018662#s5 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • MHC class II molecules (MHC II) play a pivotal role in the cell-surface presentation of antigens for surveillance by T cells. Antigen loading takes place inside the cell in endosomal compartments and loss of the peptide ligand rapidly leads to the formation of a non-receptive state of the MHC molecule. Non-receptiveness hinders the efficient loading of new antigens onto the empty MHC II. However, the mechanisms driving the formation of the peptide inaccessible state are not well understood. Here, a combined approach of experimental site-directed mutagenesis and computational modeling is used to reveal structural features underlying “non-receptiveness.” Molecular dynamics simulations of the human MHC II HLA-DR1 suggest a straightening of the α-helix of the β1 domain during the transition from the open to the non-receptive state. The movement is mostly confined to a hinge region conserved in all known MHC molecules. This shift causes a narrowing of the two helices flanking the binding site and results in a closure, which is further stabilized by the formation of a critical hydrogen bond between residues αQ9 and βN82. Mutagenesis experiments confirmed that replacement of either one of the two residues by alanine renders the protein highly susceptible. Notably, loading enhancement was also observed when the mutated MHC II molecules were expressed on the surface of fibroblast cells. Altogether, structural features underlying the non-receptive state of empty HLA-DR1 identified by theoretical means and experiments revealed highly conserved residues critically involved in the receptiveness of MHC II. The atomic details of rearrangements of the peptide-binding groove upon peptide loss provide insight into structure and dynamics of empty MHC II molecules and may foster rational approaches to interfere with non-receptiveness. Manipulation of peptide loading efficiency for improved peptide vaccination strategies could be one of the applications profiting from the structural knowledge provided by this study.
1000 Sacherschließung
lokal Major histocompatibility complex
lokal Molecular structure
lokal Peptides
lokal Molecular dynamics
lokal Simulation and modeling
lokal T cells
lokal Biochemical simulations
lokal Crystal structure
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/UnVwcCwgQmVybmQ=|https://frl.publisso.de/adhoc/creator/TWFraG1vb3IsIFRhbGF0|https://frl.publisso.de/adhoc/creator/RGlja2hhdXQsIEthdGhhcmluYQ==|https://frl.publisso.de/adhoc/creator/R3VwdGEsIFNoYXNoYW5r|https://frl.publisso.de/adhoc/creator/Q2hvdWRoYXJ5LCBJcWJhbA==|https://frl.publisso.de/adhoc/creator/V2llc23DvGxsZXIsIEthcmwtSGVpbno=|https://frl.publisso.de/adhoc/creator/SnVuZywgR8O8bnRoZXI=|https://frl.publisso.de/adhoc/creator/RnJldW5kLCBDaHJpc3RpYW4=|https://frl.publisso.de/adhoc/creator/RmFsaywgS2lyc3Rlbg==|https://frl.publisso.de/adhoc/creator/UsO2dHpzY2hrZSwgT2xhZg==|https://frl.publisso.de/adhoc/creator/S8O8aG5lLCBSb25hbGQ=|http://orcid.org/0000-0003-2254-7560|http://orcid.org/0000-0002-7329-6653
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1000 @id frl:6403342.rdf
1000 Erstellt am 2017-07-04T11:31:58.193+0200
1000 Erstellt von 21
1000 beschreibt frl:6403342
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Mon May 07 11:36:58 CEST 2018
1000 Objekt bearb. Mon May 07 11:36:58 CEST 2018
1000 Vgl. frl:6403342
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403342 |
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