Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme
ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis o...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2011-02, Vol.186 (4), p.1909-1913 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1913 |
|---|---|
| container_issue | 4 |
| container_start_page | 1909 |
| container_title | The Journal of immunology (1950) |
| container_volume | 186 |
| creator | Evnouchidou, Irini Kamal, Ram P Seregin, Sergey S Goto, Yoshikuni Tsujimoto, Masafumi Hattori, Akira Voulgari, Paraskevi V Drosos, Alexandros A Amalfitano, Andrea York, Ian A Stratikos, Efstratios |
| description | ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity and ERAP1-mediated Ag processing. To investigate this possibility, we analyzed the effect that disease-linked SNPs have on Ag processing by ERAP1 in vitro. Michaelis-Menten analysis revealed that the presence of SNPs affects the Michaelis constant and turnover number of the enzyme. Strikingly, specific ERAP1 allele-substrate combinations deviate from standard Michaelis-Menten behavior, demonstrating substrate-inhibition kinetics; to our knowledge, this phenomenon has not been described for this enzyme. Cell-based Ag-presentation analysis was consistent with changes in the substrate inhibition constant K(i), further supporting that ERAP1 allelic composition may affect Ag processing in vivo. We propose that these phenomena should be taken into account when evaluating the possible link between Ag processing and autoimmunity. |
| doi_str_mv | 10.4049/jimmunol.1003337 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4039038</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>907157737</sourcerecordid><originalsourceid>FETCH-LOGICAL-c493t-d8403b4338272a8f7a98853d1564254f80534b68cc3c51947271bbdb755b42b23</originalsourceid><addsrcrecordid>eNpVUU1v1DAQjRCIbgt3Tsg3Tin-jBMOSGhVKFIlLnC2HGey68ofwXYqLX-Qv4WX3VZw8Xg07715mtc0bwi-5pgP7--t92uI7ppgzBiTz5oNEQK3XYe7580GY0pbIjt50VzmfI8x7jDlL5sLSiingshN83u7lmLDDt1MO_iAtnE6Nrk-DlBYjYNY7ARoie7gY1r2NvuM4owgTHFxOntrUIJizepWj7S3IS6wVI7OgAgyOiA9z2AK0qHYHYSKPwEA1Q6SLjYGZAN6sCVFNB7qf3YrBHN0MupcCRB-HXwFVmqq8qlY-Gui7OE0g1fNi1m7DK_P9ar58fnm-_a2vfv25ev2011r-MBKO_Ucs5Ez1lNJdT9LPfS9YBMRXT0In3ssGB-73hhmBBm4pJKM4zRKIUZOR8qumo8n3WUdPUwGQknaqSVZr9NBRW3V_5Ng92oXH1TdO2DWV4F3Z4EUf66Qi_I2G3BOB4hrVgOWREjJZEXiE9KkmHOC-WkLweoYv3qMX53jr5S3_7p7Ijzmzf4A9IW0Gg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>907157737</pqid></control><display><type>article</type><title>Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Evnouchidou, Irini ; Kamal, Ram P ; Seregin, Sergey S ; Goto, Yoshikuni ; Tsujimoto, Masafumi ; Hattori, Akira ; Voulgari, Paraskevi V ; Drosos, Alexandros A ; Amalfitano, Andrea ; York, Ian A ; Stratikos, Efstratios</creator><creatorcontrib>Evnouchidou, Irini ; Kamal, Ram P ; Seregin, Sergey S ; Goto, Yoshikuni ; Tsujimoto, Masafumi ; Hattori, Akira ; Voulgari, Paraskevi V ; Drosos, Alexandros A ; Amalfitano, Andrea ; York, Ian A ; Stratikos, Efstratios</creatorcontrib><description>ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity and ERAP1-mediated Ag processing. To investigate this possibility, we analyzed the effect that disease-linked SNPs have on Ag processing by ERAP1 in vitro. Michaelis-Menten analysis revealed that the presence of SNPs affects the Michaelis constant and turnover number of the enzyme. Strikingly, specific ERAP1 allele-substrate combinations deviate from standard Michaelis-Menten behavior, demonstrating substrate-inhibition kinetics; to our knowledge, this phenomenon has not been described for this enzyme. Cell-based Ag-presentation analysis was consistent with changes in the substrate inhibition constant K(i), further supporting that ERAP1 allelic composition may affect Ag processing in vivo. We propose that these phenomena should be taken into account when evaluating the possible link between Ag processing and autoimmunity.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1003337</identifier><identifier>PMID: 21242517</identifier><language>eng</language><publisher>United States</publisher><subject>5' Untranslated Regions - immunology ; Alleles ; Amino Acid Substitution - genetics ; Aminopeptidases - genetics ; Aminopeptidases - metabolism ; Aminopeptidases - physiology ; Antigen Presentation - genetics ; Antigens - biosynthesis ; Arginine - genetics ; Cell Line ; Endoplasmic Reticulum - enzymology ; Endoplasmic Reticulum - genetics ; Endoplasmic Reticulum - immunology ; Glutamine - genetics ; HeLa Cells ; HLA-A Antigens - genetics ; HLA-A Antigens - metabolism ; HLA-B27 Antigen - metabolism ; Humans ; Lysine - genetics ; Minor Histocompatibility Antigens ; Peptide Biosynthesis - genetics ; Peptide Biosynthesis - immunology ; Peptide Fragments - genetics ; Peptide Fragments - metabolism ; Polymorphism, Single Nucleotide - immunology ; Substrate Specificity - genetics</subject><ispartof>The Journal of immunology (1950), 2011-02, Vol.186 (4), p.1909-1913</ispartof><rights>Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-d8403b4338272a8f7a98853d1564254f80534b68cc3c51947271bbdb755b42b23</citedby><cites>FETCH-LOGICAL-c493t-d8403b4338272a8f7a98853d1564254f80534b68cc3c51947271bbdb755b42b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21242517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Evnouchidou, Irini</creatorcontrib><creatorcontrib>Kamal, Ram P</creatorcontrib><creatorcontrib>Seregin, Sergey S</creatorcontrib><creatorcontrib>Goto, Yoshikuni</creatorcontrib><creatorcontrib>Tsujimoto, Masafumi</creatorcontrib><creatorcontrib>Hattori, Akira</creatorcontrib><creatorcontrib>Voulgari, Paraskevi V</creatorcontrib><creatorcontrib>Drosos, Alexandros A</creatorcontrib><creatorcontrib>Amalfitano, Andrea</creatorcontrib><creatorcontrib>York, Ian A</creatorcontrib><creatorcontrib>Stratikos, Efstratios</creatorcontrib><title>Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity and ERAP1-mediated Ag processing. To investigate this possibility, we analyzed the effect that disease-linked SNPs have on Ag processing by ERAP1 in vitro. Michaelis-Menten analysis revealed that the presence of SNPs affects the Michaelis constant and turnover number of the enzyme. Strikingly, specific ERAP1 allele-substrate combinations deviate from standard Michaelis-Menten behavior, demonstrating substrate-inhibition kinetics; to our knowledge, this phenomenon has not been described for this enzyme. Cell-based Ag-presentation analysis was consistent with changes in the substrate inhibition constant K(i), further supporting that ERAP1 allelic composition may affect Ag processing in vivo. We propose that these phenomena should be taken into account when evaluating the possible link between Ag processing and autoimmunity.</description><subject>5' Untranslated Regions - immunology</subject><subject>Alleles</subject><subject>Amino Acid Substitution - genetics</subject><subject>Aminopeptidases - genetics</subject><subject>Aminopeptidases - metabolism</subject><subject>Aminopeptidases - physiology</subject><subject>Antigen Presentation - genetics</subject><subject>Antigens - biosynthesis</subject><subject>Arginine - genetics</subject><subject>Cell Line</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Endoplasmic Reticulum - genetics</subject><subject>Endoplasmic Reticulum - immunology</subject><subject>Glutamine - genetics</subject><subject>HeLa Cells</subject><subject>HLA-A Antigens - genetics</subject><subject>HLA-A Antigens - metabolism</subject><subject>HLA-B27 Antigen - metabolism</subject><subject>Humans</subject><subject>Lysine - genetics</subject><subject>Minor Histocompatibility Antigens</subject><subject>Peptide Biosynthesis - genetics</subject><subject>Peptide Biosynthesis - immunology</subject><subject>Peptide Fragments - genetics</subject><subject>Peptide Fragments - metabolism</subject><subject>Polymorphism, Single Nucleotide - immunology</subject><subject>Substrate Specificity - genetics</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1v1DAQjRCIbgt3Tsg3Tin-jBMOSGhVKFIlLnC2HGey68ofwXYqLX-Qv4WX3VZw8Xg07715mtc0bwi-5pgP7--t92uI7ppgzBiTz5oNEQK3XYe7580GY0pbIjt50VzmfI8x7jDlL5sLSiingshN83u7lmLDDt1MO_iAtnE6Nrk-DlBYjYNY7ARoie7gY1r2NvuM4owgTHFxOntrUIJizepWj7S3IS6wVI7OgAgyOiA9z2AK0qHYHYSKPwEA1Q6SLjYGZAN6sCVFNB7qf3YrBHN0MupcCRB-HXwFVmqq8qlY-Gui7OE0g1fNi1m7DK_P9ar58fnm-_a2vfv25ev2011r-MBKO_Ucs5Ez1lNJdT9LPfS9YBMRXT0In3ssGB-73hhmBBm4pJKM4zRKIUZOR8qumo8n3WUdPUwGQknaqSVZr9NBRW3V_5Ng92oXH1TdO2DWV4F3Z4EUf66Qi_I2G3BOB4hrVgOWREjJZEXiE9KkmHOC-WkLweoYv3qMX53jr5S3_7p7Ijzmzf4A9IW0Gg</recordid><startdate>20110215</startdate><enddate>20110215</enddate><creator>Evnouchidou, Irini</creator><creator>Kamal, Ram P</creator><creator>Seregin, Sergey S</creator><creator>Goto, Yoshikuni</creator><creator>Tsujimoto, Masafumi</creator><creator>Hattori, Akira</creator><creator>Voulgari, Paraskevi V</creator><creator>Drosos, Alexandros A</creator><creator>Amalfitano, Andrea</creator><creator>York, Ian A</creator><creator>Stratikos, Efstratios</creator><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>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20110215</creationdate><title>Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme</title><author>Evnouchidou, Irini ; Kamal, Ram P ; Seregin, Sergey S ; Goto, Yoshikuni ; Tsujimoto, Masafumi ; Hattori, Akira ; Voulgari, Paraskevi V ; Drosos, Alexandros A ; Amalfitano, Andrea ; York, Ian A ; Stratikos, Efstratios</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-d8403b4338272a8f7a98853d1564254f80534b68cc3c51947271bbdb755b42b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>5' Untranslated Regions - immunology</topic><topic>Alleles</topic><topic>Amino Acid Substitution - genetics</topic><topic>Aminopeptidases - genetics</topic><topic>Aminopeptidases - metabolism</topic><topic>Aminopeptidases - physiology</topic><topic>Antigen Presentation - genetics</topic><topic>Antigens - biosynthesis</topic><topic>Arginine - genetics</topic><topic>Cell Line</topic><topic>Endoplasmic Reticulum - enzymology</topic><topic>Endoplasmic Reticulum - genetics</topic><topic>Endoplasmic Reticulum - immunology</topic><topic>Glutamine - genetics</topic><topic>HeLa Cells</topic><topic>HLA-A Antigens - genetics</topic><topic>HLA-A Antigens - metabolism</topic><topic>HLA-B27 Antigen - metabolism</topic><topic>Humans</topic><topic>Lysine - genetics</topic><topic>Minor Histocompatibility Antigens</topic><topic>Peptide Biosynthesis - genetics</topic><topic>Peptide Biosynthesis - immunology</topic><topic>Peptide Fragments - genetics</topic><topic>Peptide Fragments - metabolism</topic><topic>Polymorphism, Single Nucleotide - immunology</topic><topic>Substrate Specificity - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Evnouchidou, Irini</creatorcontrib><creatorcontrib>Kamal, Ram P</creatorcontrib><creatorcontrib>Seregin, Sergey S</creatorcontrib><creatorcontrib>Goto, Yoshikuni</creatorcontrib><creatorcontrib>Tsujimoto, Masafumi</creatorcontrib><creatorcontrib>Hattori, Akira</creatorcontrib><creatorcontrib>Voulgari, Paraskevi V</creatorcontrib><creatorcontrib>Drosos, Alexandros A</creatorcontrib><creatorcontrib>Amalfitano, Andrea</creatorcontrib><creatorcontrib>York, Ian A</creatorcontrib><creatorcontrib>Stratikos, Efstratios</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Evnouchidou, Irini</au><au>Kamal, Ram P</au><au>Seregin, Sergey S</au><au>Goto, Yoshikuni</au><au>Tsujimoto, Masafumi</au><au>Hattori, Akira</au><au>Voulgari, Paraskevi V</au><au>Drosos, Alexandros A</au><au>Amalfitano, Andrea</au><au>York, Ian A</au><au>Stratikos, Efstratios</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2011-02-15</date><risdate>2011</risdate><volume>186</volume><issue>4</issue><spage>1909</spage><epage>1913</epage><pages>1909-1913</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity and ERAP1-mediated Ag processing. To investigate this possibility, we analyzed the effect that disease-linked SNPs have on Ag processing by ERAP1 in vitro. Michaelis-Menten analysis revealed that the presence of SNPs affects the Michaelis constant and turnover number of the enzyme. Strikingly, specific ERAP1 allele-substrate combinations deviate from standard Michaelis-Menten behavior, demonstrating substrate-inhibition kinetics; to our knowledge, this phenomenon has not been described for this enzyme. Cell-based Ag-presentation analysis was consistent with changes in the substrate inhibition constant K(i), further supporting that ERAP1 allelic composition may affect Ag processing in vivo. We propose that these phenomena should be taken into account when evaluating the possible link between Ag processing and autoimmunity.</abstract><cop>United States</cop><pmid>21242517</pmid><doi>10.4049/jimmunol.1003337</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2011-02, Vol.186 (4), p.1909-1913 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4039038 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 5' Untranslated Regions - immunology Alleles Amino Acid Substitution - genetics Aminopeptidases - genetics Aminopeptidases - metabolism Aminopeptidases - physiology Antigen Presentation - genetics Antigens - biosynthesis Arginine - genetics Cell Line Endoplasmic Reticulum - enzymology Endoplasmic Reticulum - genetics Endoplasmic Reticulum - immunology Glutamine - genetics HeLa Cells HLA-A Antigens - genetics HLA-A Antigens - metabolism HLA-B27 Antigen - metabolism Humans Lysine - genetics Minor Histocompatibility Antigens Peptide Biosynthesis - genetics Peptide Biosynthesis - immunology Peptide Fragments - genetics Peptide Fragments - metabolism Polymorphism, Single Nucleotide - immunology Substrate Specificity - genetics |
| title | Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T16%3A59%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cutting%20Edge:%20Coding%20single%20nucleotide%20polymorphisms%20of%20endoplasmic%20reticulum%20aminopeptidase%201%20can%20affect%20antigenic%20peptide%20generation%20in%20vitro%20by%20influencing%20basic%20enzymatic%20properties%20of%20the%20enzyme&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Evnouchidou,%20Irini&rft.date=2011-02-15&rft.volume=186&rft.issue=4&rft.spage=1909&rft.epage=1913&rft.pages=1909-1913&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.1003337&rft_dat=%3Cproquest_pubme%3E907157737%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=907157737&rft_id=info:pmid/21242517&rfr_iscdi=true |