Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction
Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Ga...
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Veröffentlicht in: | The Journal of biological chemistry 2016-01, Vol.291 (4), p.1890-1904 |
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creator | Gu, Xiaodong Huang, Ying Levison, Bruce S. Gerstenecker, Gary DiDonato, Anthony J. Hazen, Leah B. Lee, Joonsue Gogonea, Valentin DiDonato, Joseph A. Hazen, Stanley L. |
description | Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes or lipoproteins. |
doi_str_mv | 10.1074/jbc.M115.678334 |
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We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes or lipoproteins.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M115.678334</identifier><identifier>PMID: 26567339</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Motifs ; apolipoprotein A-I ; Apolipoprotein A-I - genetics ; Apolipoprotein A-I - metabolism ; Aryldialkylphosphatase - chemistry ; Aryldialkylphosphatase - genetics ; Aryldialkylphosphatase - metabolism ; Catalysis ; click chemistry ; Crystallography, X-Ray ; high density lipoprotein (HDL) ; Humans ; Lipids ; Lipoproteins, HDL - metabolism ; Mutagenesis, Site-Directed ; paraoxonase 1 ; phospholipid ; photoactivatable phospholipid ; photoaffinity labeling ; pon1 ; Protein Binding ; protein-lipid interaction ; protein-lipid interactions</subject><ispartof>The Journal of biological chemistry, 2016-01, Vol.291 (4), p.1890-1904</ispartof><rights>2016 © 2016 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2016 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>2016 by The American Society for Biochemistry and Molecular Biology, Inc. 2016 The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-e5acf6f16efd1a96974acf5f002275fe7ac4cb0b871fd746bbafeb8ea819aebd3</citedby><cites>FETCH-LOGICAL-c443t-e5acf6f16efd1a96974acf5f002275fe7ac4cb0b871fd746bbafeb8ea819aebd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722466/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722466/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26567339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gu, Xiaodong</creatorcontrib><creatorcontrib>Huang, Ying</creatorcontrib><creatorcontrib>Levison, Bruce S.</creatorcontrib><creatorcontrib>Gerstenecker, Gary</creatorcontrib><creatorcontrib>DiDonato, Anthony J.</creatorcontrib><creatorcontrib>Hazen, Leah B.</creatorcontrib><creatorcontrib>Lee, Joonsue</creatorcontrib><creatorcontrib>Gogonea, Valentin</creatorcontrib><creatorcontrib>DiDonato, Joseph A.</creatorcontrib><creatorcontrib>Hazen, Stanley L.</creatorcontrib><title>Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes or lipoproteins.</description><subject>Amino Acid Motifs</subject><subject>apolipoprotein A-I</subject><subject>Apolipoprotein A-I - genetics</subject><subject>Apolipoprotein A-I - metabolism</subject><subject>Aryldialkylphosphatase - chemistry</subject><subject>Aryldialkylphosphatase - genetics</subject><subject>Aryldialkylphosphatase - metabolism</subject><subject>Catalysis</subject><subject>click chemistry</subject><subject>Crystallography, X-Ray</subject><subject>high density lipoprotein (HDL)</subject><subject>Humans</subject><subject>Lipids</subject><subject>Lipoproteins, HDL - metabolism</subject><subject>Mutagenesis, Site-Directed</subject><subject>paraoxonase 1</subject><subject>phospholipid</subject><subject>photoactivatable phospholipid</subject><subject>photoaffinity labeling</subject><subject>pon1</subject><subject>Protein Binding</subject><subject>protein-lipid interaction</subject><subject>protein-lipid interactions</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kFtLAzEQhYMotl6efZP8ga2b3Wyy-yJIvRUqiij4FnKZ2JQ2Kcla9N-bUhV9cF7CZM58wzkInZByREpOz-ZKj-4IaUaMt3VNd9CQlG1d1A152UXDsqxI0VVNO0AHKc3LXLQj-2hQsYbxuu6GSE0M-N5Zp2XvgsfB4nF0fW4X-EFGGd6DlwkwwY-QnHmDhCd-HRZrMNh5fOteZ_gSfHL9B566VVjF0EMeTHwPUeoN8wjtWblIcPz1HqLn66un8W0xvb-ZjC-mhaa07gtopLbMEgbWENmxjtP80dhsouKNBS411apULSfWcMqUkhZUC7IlnQRl6kN0vuWu3tQSjM6-olyIVXRLGT9EkE78nXg3E69hLSivKspYBpxtATqGlCLYn11Sik3cIsctNnGLbdx54_T3yR_9d75Z0G0FkI2vHUSRtAOvwbgIuhcmuH_hn2BNk40</recordid><startdate>20160122</startdate><enddate>20160122</enddate><creator>Gu, Xiaodong</creator><creator>Huang, Ying</creator><creator>Levison, Bruce S.</creator><creator>Gerstenecker, Gary</creator><creator>DiDonato, Anthony J.</creator><creator>Hazen, Leah B.</creator><creator>Lee, Joonsue</creator><creator>Gogonea, Valentin</creator><creator>DiDonato, Joseph A.</creator><creator>Hazen, Stanley L.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20160122</creationdate><title>Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction</title><author>Gu, Xiaodong ; Huang, Ying ; Levison, Bruce S. ; Gerstenecker, Gary ; DiDonato, Anthony J. ; Hazen, Leah B. ; Lee, Joonsue ; Gogonea, Valentin ; DiDonato, Joseph A. ; Hazen, Stanley L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-e5acf6f16efd1a96974acf5f002275fe7ac4cb0b871fd746bbafeb8ea819aebd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amino Acid Motifs</topic><topic>apolipoprotein A-I</topic><topic>Apolipoprotein A-I - genetics</topic><topic>Apolipoprotein A-I - metabolism</topic><topic>Aryldialkylphosphatase - chemistry</topic><topic>Aryldialkylphosphatase - genetics</topic><topic>Aryldialkylphosphatase - metabolism</topic><topic>Catalysis</topic><topic>click chemistry</topic><topic>Crystallography, X-Ray</topic><topic>high density lipoprotein (HDL)</topic><topic>Humans</topic><topic>Lipids</topic><topic>Lipoproteins, HDL - metabolism</topic><topic>Mutagenesis, Site-Directed</topic><topic>paraoxonase 1</topic><topic>phospholipid</topic><topic>photoactivatable phospholipid</topic><topic>photoaffinity labeling</topic><topic>pon1</topic><topic>Protein Binding</topic><topic>protein-lipid interaction</topic><topic>protein-lipid interactions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gu, Xiaodong</creatorcontrib><creatorcontrib>Huang, Ying</creatorcontrib><creatorcontrib>Levison, Bruce S.</creatorcontrib><creatorcontrib>Gerstenecker, Gary</creatorcontrib><creatorcontrib>DiDonato, Anthony J.</creatorcontrib><creatorcontrib>Hazen, Leah B.</creatorcontrib><creatorcontrib>Lee, Joonsue</creatorcontrib><creatorcontrib>Gogonea, Valentin</creatorcontrib><creatorcontrib>DiDonato, Joseph A.</creatorcontrib><creatorcontrib>Hazen, Stanley L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gu, Xiaodong</au><au>Huang, Ying</au><au>Levison, Bruce S.</au><au>Gerstenecker, Gary</au><au>DiDonato, Anthony J.</au><au>Hazen, Leah B.</au><au>Lee, Joonsue</au><au>Gogonea, Valentin</au><au>DiDonato, Joseph A.</au><au>Hazen, Stanley L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2016-01-22</date><risdate>2016</risdate><volume>291</volume><issue>4</issue><spage>1890</spage><epage>1904</epage><pages>1890-1904</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes or lipoproteins.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26567339</pmid><doi>10.1074/jbc.M115.678334</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Motifs apolipoprotein A-I Apolipoprotein A-I - genetics Apolipoprotein A-I - metabolism Aryldialkylphosphatase - chemistry Aryldialkylphosphatase - genetics Aryldialkylphosphatase - metabolism Catalysis click chemistry Crystallography, X-Ray high density lipoprotein (HDL) Humans Lipids Lipoproteins, HDL - metabolism Mutagenesis, Site-Directed paraoxonase 1 phospholipid photoactivatable phospholipid photoaffinity labeling pon1 Protein Binding protein-lipid interaction protein-lipid interactions |
title | Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction |
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