A Glycopeptide in Complex with MHC Class I Uses the GalNAc Residue as an Anchor
Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showe...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2003-12, Vol.100 (25), p.15029-15034 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Apostolopoulos, Vasso Yuriev, Elizabeth Ramsland, Paul A. Halton, Jodie Osinski, Carla Li, Wenjun Plebanski, Magdalena Paulsen, Hans Ian F. C. Mc Kenzie |
| description | Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showed that the central P5-Thr-GalNAc residue points into the C pocket and forms van der Waals and hydrogen bond interactions with the MHC class I. As predicted, GalNAc, a modified peptide carrying an additional anchor in the central C anchor pocket, increased the affinity by ≈100-fold compared with the native low-affinity peptide (MUC1-8). The findings demonstrate that glycopeptides associated with MHC class I molecules can use GalNAc to anchor the peptide in the groove and enable high-affinity binding. |
| doi_str_mv | 10.1073/pnas.2432220100 |
| format | Article |
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The findings demonstrate that glycopeptides associated with MHC class I molecules can use GalNAc to anchor the peptide in the groove and enable high-affinity binding.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2432220100</identifier><identifier>PMID: 14657390</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Acetylgalactosamine - chemistry ; Amino acids ; Animals ; Antigens ; Binding Sites ; Biological Sciences ; Crystal structure ; Cultured cells ; Enzyme-Linked Immunosorbent Assay ; Female ; Genes, MHC Class I ; Glycopeptides ; Glycopeptides - chemistry ; Hydrogen Bonding ; Hydrogen bonds ; Immunology ; Interferon-gamma - metabolism ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Molecular interactions ; Molecules ; Peptides ; Peptides - chemistry ; Protein Binding ; Protein Structure, Secondary ; T cell antigen receptors ; T lymphocytes ; T lymphoid precursor cells ; Temperature ; Time Factors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2003-12, Vol.100 (25), p.15029-15034</ispartof><rights>Copyright 1993-2003 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Dec 9, 2003</rights><rights>Copyright © 2003, The National Academy of Sciences 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4410-dc463bfbb8bd3884b02334984783197f27022cf3d40d529875221e05ee0f7ac93</citedby><cites>FETCH-LOGICAL-c4410-dc463bfbb8bd3884b02334984783197f27022cf3d40d529875221e05ee0f7ac93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/100/25.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3148555$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3148555$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14657390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Apostolopoulos, Vasso</creatorcontrib><creatorcontrib>Yuriev, Elizabeth</creatorcontrib><creatorcontrib>Ramsland, Paul A.</creatorcontrib><creatorcontrib>Halton, Jodie</creatorcontrib><creatorcontrib>Osinski, Carla</creatorcontrib><creatorcontrib>Li, Wenjun</creatorcontrib><creatorcontrib>Plebanski, Magdalena</creatorcontrib><creatorcontrib>Paulsen, Hans</creatorcontrib><creatorcontrib>Ian F. C. Mc Kenzie</creatorcontrib><title>A Glycopeptide in Complex with MHC Class I Uses the GalNAc Residue as an Anchor</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showed that the central P5-Thr-GalNAc residue points into the C pocket and forms van der Waals and hydrogen bond interactions with the MHC class I. As predicted, GalNAc, a modified peptide carrying an additional anchor in the central C anchor pocket, increased the affinity by ≈100-fold compared with the native low-affinity peptide (MUC1-8). The findings demonstrate that glycopeptides associated with MHC class I molecules can use GalNAc to anchor the peptide in the groove and enable high-affinity binding.</description><subject>Acetylgalactosamine - chemistry</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antigens</subject><subject>Binding Sites</subject><subject>Biological Sciences</subject><subject>Crystal structure</subject><subject>Cultured cells</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Genes, MHC Class I</subject><subject>Glycopeptides</subject><subject>Glycopeptides - chemistry</subject><subject>Hydrogen Bonding</subject><subject>Hydrogen bonds</subject><subject>Immunology</subject><subject>Interferon-gamma - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Molecular</subject><subject>Molecular interactions</subject><subject>Molecules</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Protein Binding</subject><subject>Protein Structure, Secondary</subject><subject>T cell antigen receptors</subject><subject>T lymphocytes</subject><subject>T lymphoid precursor cells</subject><subject>Temperature</subject><subject>Time Factors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0bFv1DAUBnALgehRmFkQshgqMaR9frZje2A4ReVaqVAJ0dlyEofLyReHOIH2vyenO_WApZMH_74n-32EvGVwzkDxi75z6RwFR0RgAM_IgoFhWS4MPCcLAFSZFihOyKuUNgBgpIaX5ISJXCpuYEFul3QVHqrY-35sa0_bjhZx2wd_T3-345p-uSpoEVxK9JreJZ_ouPZ05cLXZUW_-dTWk6cuUdfRZVet4_CavGhcSP7N4Twld58vvxdX2c3t6rpY3mSVEAyyuhI5L5uy1GXNtRYlIOfCaKE0Z0Y1qACxangtoJZotJKIzIP0HhrlKsNPyaf93H4qt76ufDcOLth-aLdueLDRtfbfm65d2x_xl0VjtME5f3bID_Hn5NNot22qfAiu83FKVjEhhMz1k5AZzDUTaoYf_oObOA3dvAQ7d4Nao5YzutijaogpDb55fDEDu2vU7hq1x0bnxPu_P3r0hwpn8PEAdsnjOLAoLZOAxjZTCKO_H2dLn7AzebcnmzTG4dFwJrSUkv8BcYq7cA</recordid><startdate>20031209</startdate><enddate>20031209</enddate><creator>Apostolopoulos, Vasso</creator><creator>Yuriev, Elizabeth</creator><creator>Ramsland, Paul A.</creator><creator>Halton, Jodie</creator><creator>Osinski, Carla</creator><creator>Li, Wenjun</creator><creator>Plebanski, Magdalena</creator><creator>Paulsen, Hans</creator><creator>Ian F. C. Mc Kenzie</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20031209</creationdate><title>A Glycopeptide in Complex with MHC Class I Uses the GalNAc Residue as an Anchor</title><author>Apostolopoulos, Vasso ; Yuriev, Elizabeth ; Ramsland, Paul A. ; Halton, Jodie ; Osinski, Carla ; Li, Wenjun ; Plebanski, Magdalena ; Paulsen, Hans ; Ian F. C. 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C. Mc Kenzie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Glycopeptide in Complex with MHC Class I Uses the GalNAc Residue as an Anchor</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2003-12-09</date><risdate>2003</risdate><volume>100</volume><issue>25</issue><spage>15029</spage><epage>15034</epage><pages>15029-15034</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showed that the central P5-Thr-GalNAc residue points into the C pocket and forms van der Waals and hydrogen bond interactions with the MHC class I. As predicted, GalNAc, a modified peptide carrying an additional anchor in the central C anchor pocket, increased the affinity by ≈100-fold compared with the native low-affinity peptide (MUC1-8). The findings demonstrate that glycopeptides associated with MHC class I molecules can use GalNAc to anchor the peptide in the groove and enable high-affinity binding.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14657390</pmid><doi>10.1073/pnas.2432220100</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylgalactosamine - chemistry Amino acids Animals Antigens Binding Sites Biological Sciences Crystal structure Cultured cells Enzyme-Linked Immunosorbent Assay Female Genes, MHC Class I Glycopeptides Glycopeptides - chemistry Hydrogen Bonding Hydrogen bonds Immunology Interferon-gamma - metabolism Mice Mice, Inbred C57BL Models, Molecular Molecular interactions Molecules Peptides Peptides - chemistry Protein Binding Protein Structure, Secondary T cell antigen receptors T lymphocytes T lymphoid precursor cells Temperature Time Factors |
| title | A Glycopeptide in Complex with MHC Class I Uses the GalNAc Residue as an Anchor |
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