cAMP-dependent Protein Kinase Phosphorylation Produces Interdomain Movement in SUR2B Leading to Activation of the Vascular KATP Channel
Vascular ATP-sensitive K+ channels are activated by multiple vasodilating hormones and neurotransmitters via PKA. A critical PKA phosphorylation site (Ser-1387) is found in the second nucleotide-binding domain (NBD2) of the SUR2B subunit. To understand how phosphorylation at Ser-1387 leads to change...
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| Veröffentlicht in: | The Journal of biological chemistry 2008-03, Vol.283 (12), p.7523-7530 |
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| creator | Shi, Yun Chen, Xianfeng Wu, Zhongying Shi, Weiwei Yang, Yang Cui, Ningren Jiang, Chun Harrison, Robert W. |
| description | Vascular ATP-sensitive K+ channels are activated by multiple vasodilating hormones and neurotransmitters via PKA. A critical PKA phosphorylation site (Ser-1387) is found in the second nucleotide-binding domain (NBD2) of the SUR2B subunit. To understand how phosphorylation at Ser-1387 leads to changes in channel activity, we modeled the SUR2B using a newly crystallized ABC protein SAV1866. The model showed that Ser-1387 was located on the interface of NBD2 with TMD1 and physically interacted with Tyr-506 in TMD1. A positively charged residue (Arg-1462) in NBD2 was revealed in the close vicinity of Ser-1387. Mutation of either of these three residues abolished PKA-dependent channel activation. Molecular dynamics simulations suggested that Ser-1387, Tyr-506, and Arg-1462 formed a compact triad upon Ser-1387 phosphorylation, leading to reshaping of the NBD2 interface and movements of NBD2 and TMD1. Restriction of the interdomain movements by engineering a disulfide bond between TMD1 and NBD2 prevented the channel activation in a redox-dependent manner. Thus, a channel-gating mechanism is suggested through enhancing the NBD-TMD coupling efficiency following Ser-1387 phosphorylation, which is shared by multiple vasodilators. |
| doi_str_mv | 10.1074/jbc.M709941200 |
| format | Article |
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A critical PKA phosphorylation site (Ser-1387) is found in the second nucleotide-binding domain (NBD2) of the SUR2B subunit. To understand how phosphorylation at Ser-1387 leads to changes in channel activity, we modeled the SUR2B using a newly crystallized ABC protein SAV1866. The model showed that Ser-1387 was located on the interface of NBD2 with TMD1 and physically interacted with Tyr-506 in TMD1. A positively charged residue (Arg-1462) in NBD2 was revealed in the close vicinity of Ser-1387. Mutation of either of these three residues abolished PKA-dependent channel activation. Molecular dynamics simulations suggested that Ser-1387, Tyr-506, and Arg-1462 formed a compact triad upon Ser-1387 phosphorylation, leading to reshaping of the NBD2 interface and movements of NBD2 and TMD1. Restriction of the interdomain movements by engineering a disulfide bond between TMD1 and NBD2 prevented the channel activation in a redox-dependent manner. Thus, a channel-gating mechanism is suggested through enhancing the NBD-TMD coupling efficiency following Ser-1387 phosphorylation, which is shared by multiple vasodilators.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M709941200</identifier><identifier>PMID: 18198173</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Substitution ; Animals ; ATP-Binding Cassette Transporters - chemistry ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Cyclic AMP-Dependent Protein Kinases - chemistry ; Cyclic AMP-Dependent Protein Kinases - genetics ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Disulfides - chemistry ; Disulfides - metabolism ; KATP Channels - chemistry ; KATP Channels - genetics ; KATP Channels - metabolism ; Membrane Transport, Structure, Function, and Biogenesis ; Models, Molecular ; Muscle, Smooth, Vascular - chemistry ; Muscle, Smooth, Vascular - metabolism ; Oxidation-Reduction ; Phosphorylation ; Potassium Channels - chemistry ; Potassium Channels - genetics ; Potassium Channels - metabolism ; Potassium Channels, Inwardly Rectifying - chemistry ; Potassium Channels, Inwardly Rectifying - genetics ; Potassium Channels, Inwardly Rectifying - metabolism ; Protein Structure, Tertiary - physiology ; Rats ; Receptors, Drug - chemistry ; Receptors, Drug - genetics ; Receptors, Drug - metabolism ; Sulfonylurea Receptors</subject><ispartof>The Journal of biological chemistry, 2008-03, Vol.283 (12), p.7523-7530</ispartof><rights>2008 © 2008 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>Copyright © 2008, 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-c4040-34dbd7f04d81faaafd3491f4562ef72e4223d36221e9d5a8d2d99b71b17154923</citedby><cites>FETCH-LOGICAL-c4040-34dbd7f04d81faaafd3491f4562ef72e4223d36221e9d5a8d2d99b71b17154923</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/PMC2276326/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276326/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18198173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Yun</creatorcontrib><creatorcontrib>Chen, Xianfeng</creatorcontrib><creatorcontrib>Wu, Zhongying</creatorcontrib><creatorcontrib>Shi, Weiwei</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Cui, Ningren</creatorcontrib><creatorcontrib>Jiang, Chun</creatorcontrib><creatorcontrib>Harrison, Robert W.</creatorcontrib><title>cAMP-dependent Protein Kinase Phosphorylation Produces Interdomain Movement in SUR2B Leading to Activation of the Vascular KATP Channel</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Vascular ATP-sensitive K+ channels are activated by multiple vasodilating hormones and neurotransmitters via PKA. A critical PKA phosphorylation site (Ser-1387) is found in the second nucleotide-binding domain (NBD2) of the SUR2B subunit. To understand how phosphorylation at Ser-1387 leads to changes in channel activity, we modeled the SUR2B using a newly crystallized ABC protein SAV1866. The model showed that Ser-1387 was located on the interface of NBD2 with TMD1 and physically interacted with Tyr-506 in TMD1. A positively charged residue (Arg-1462) in NBD2 was revealed in the close vicinity of Ser-1387. Mutation of either of these three residues abolished PKA-dependent channel activation. Molecular dynamics simulations suggested that Ser-1387, Tyr-506, and Arg-1462 formed a compact triad upon Ser-1387 phosphorylation, leading to reshaping of the NBD2 interface and movements of NBD2 and TMD1. Restriction of the interdomain movements by engineering a disulfide bond between TMD1 and NBD2 prevented the channel activation in a redox-dependent manner. Thus, a channel-gating mechanism is suggested through enhancing the NBD-TMD coupling efficiency following Ser-1387 phosphorylation, which is shared by multiple vasodilators.</description><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>ATP-Binding Cassette Transporters - chemistry</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - chemistry</subject><subject>Cyclic AMP-Dependent Protein Kinases - genetics</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Disulfides - chemistry</subject><subject>Disulfides - metabolism</subject><subject>KATP Channels - chemistry</subject><subject>KATP Channels - genetics</subject><subject>KATP Channels - metabolism</subject><subject>Membrane Transport, Structure, Function, and Biogenesis</subject><subject>Models, Molecular</subject><subject>Muscle, Smooth, Vascular - chemistry</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Phosphorylation</subject><subject>Potassium Channels - chemistry</subject><subject>Potassium Channels - genetics</subject><subject>Potassium Channels - metabolism</subject><subject>Potassium Channels, Inwardly Rectifying - chemistry</subject><subject>Potassium Channels, Inwardly Rectifying - genetics</subject><subject>Potassium Channels, Inwardly Rectifying - metabolism</subject><subject>Protein Structure, Tertiary - physiology</subject><subject>Rats</subject><subject>Receptors, Drug - chemistry</subject><subject>Receptors, Drug - genetics</subject><subject>Receptors, Drug - metabolism</subject><subject>Sulfonylurea Receptors</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV1v0zAUhi0EYt3glkuwxHWKv9IkN0hdxce0VlRsRdxZjn3SeErsyk6L9gv2t3GUicEFvrGl87zvOccvQm8omVNSiA93tZ5vClJVgjJCnqEZJSXPeE5_PkczQhjNKpaXZ-g8xjuSjqjoS3RGS1qVtOAz9KCXm21m4ADOgBvwNvgBrMPX1qkIeNv6eGh9uO_UYL0by-aoIeIrN0AwvleJ3fgT9KM4vW9239klXoMy1u3x4PFSD_Y0iX2DhxbwDxX1sVMBXy9vt3jVKuege4VeNKqL8PrxvkC7z59uV1-z9bcvV6vlOtOCCJJxYWpTNESYkjZKqcbwtFEj8gWDpmAgGOOGLxijUJlclYaZqqoLWtOC5qJi_AJ9nHwPx7oHo9PYQXXyEGyvwr30ysp_K862cu9PkrFiwdkiGcwnAx18jAGaP1pK5BiJTJHIp0iS4O3fHZ_wxwwS8H4CWrtvf9kAsrZet9BLVnJJmSxyNlLvJqpRXqp9sFHubhihnJCyIKIciXIiIP3fyUKQUVtwGkzy1IM03v5vxt-TFLEi</recordid><startdate>20080321</startdate><enddate>20080321</enddate><creator>Shi, Yun</creator><creator>Chen, Xianfeng</creator><creator>Wu, Zhongying</creator><creator>Shi, Weiwei</creator><creator>Yang, Yang</creator><creator>Cui, Ningren</creator><creator>Jiang, Chun</creator><creator>Harrison, Robert W.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>20080321</creationdate><title>cAMP-dependent Protein Kinase Phosphorylation Produces Interdomain Movement in SUR2B Leading to Activation of the Vascular KATP Channel</title><author>Shi, Yun ; Chen, Xianfeng ; Wu, Zhongying ; Shi, Weiwei ; Yang, Yang ; Cui, Ningren ; Jiang, Chun ; Harrison, Robert W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4040-34dbd7f04d81faaafd3491f4562ef72e4223d36221e9d5a8d2d99b71b17154923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Amino Acid Substitution</topic><topic>Animals</topic><topic>ATP-Binding Cassette Transporters - chemistry</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - chemistry</topic><topic>Cyclic AMP-Dependent Protein Kinases - genetics</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Disulfides - chemistry</topic><topic>Disulfides - metabolism</topic><topic>KATP Channels - chemistry</topic><topic>KATP Channels - genetics</topic><topic>KATP Channels - metabolism</topic><topic>Membrane Transport, Structure, Function, and Biogenesis</topic><topic>Models, Molecular</topic><topic>Muscle, Smooth, Vascular - chemistry</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Phosphorylation</topic><topic>Potassium Channels - chemistry</topic><topic>Potassium Channels - genetics</topic><topic>Potassium Channels - metabolism</topic><topic>Potassium Channels, Inwardly Rectifying - chemistry</topic><topic>Potassium Channels, Inwardly Rectifying - genetics</topic><topic>Potassium Channels, Inwardly Rectifying - metabolism</topic><topic>Protein Structure, Tertiary - physiology</topic><topic>Rats</topic><topic>Receptors, Drug - chemistry</topic><topic>Receptors, Drug - genetics</topic><topic>Receptors, Drug - metabolism</topic><topic>Sulfonylurea Receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Yun</creatorcontrib><creatorcontrib>Chen, Xianfeng</creatorcontrib><creatorcontrib>Wu, Zhongying</creatorcontrib><creatorcontrib>Shi, Weiwei</creatorcontrib><creatorcontrib>Yang, Yang</creatorcontrib><creatorcontrib>Cui, Ningren</creatorcontrib><creatorcontrib>Jiang, Chun</creatorcontrib><creatorcontrib>Harrison, Robert W.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</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>Shi, Yun</au><au>Chen, Xianfeng</au><au>Wu, Zhongying</au><au>Shi, Weiwei</au><au>Yang, Yang</au><au>Cui, Ningren</au><au>Jiang, Chun</au><au>Harrison, Robert W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>cAMP-dependent Protein Kinase Phosphorylation Produces Interdomain Movement in SUR2B Leading to Activation of the Vascular KATP Channel</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2008-03-21</date><risdate>2008</risdate><volume>283</volume><issue>12</issue><spage>7523</spage><epage>7530</epage><pages>7523-7530</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Vascular ATP-sensitive K+ channels are activated by multiple vasodilating hormones and neurotransmitters via PKA. A critical PKA phosphorylation site (Ser-1387) is found in the second nucleotide-binding domain (NBD2) of the SUR2B subunit. To understand how phosphorylation at Ser-1387 leads to changes in channel activity, we modeled the SUR2B using a newly crystallized ABC protein SAV1866. The model showed that Ser-1387 was located on the interface of NBD2 with TMD1 and physically interacted with Tyr-506 in TMD1. A positively charged residue (Arg-1462) in NBD2 was revealed in the close vicinity of Ser-1387. Mutation of either of these three residues abolished PKA-dependent channel activation. Molecular dynamics simulations suggested that Ser-1387, Tyr-506, and Arg-1462 formed a compact triad upon Ser-1387 phosphorylation, leading to reshaping of the NBD2 interface and movements of NBD2 and TMD1. Restriction of the interdomain movements by engineering a disulfide bond between TMD1 and NBD2 prevented the channel activation in a redox-dependent manner. Thus, a channel-gating mechanism is suggested through enhancing the NBD-TMD coupling efficiency following Ser-1387 phosphorylation, which is shared by multiple vasodilators.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18198173</pmid><doi>10.1074/jbc.M709941200</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Substitution Animals ATP-Binding Cassette Transporters - chemistry ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Cyclic AMP-Dependent Protein Kinases - chemistry Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism Disulfides - chemistry Disulfides - metabolism KATP Channels - chemistry KATP Channels - genetics KATP Channels - metabolism Membrane Transport, Structure, Function, and Biogenesis Models, Molecular Muscle, Smooth, Vascular - chemistry Muscle, Smooth, Vascular - metabolism Oxidation-Reduction Phosphorylation Potassium Channels - chemistry Potassium Channels - genetics Potassium Channels - metabolism Potassium Channels, Inwardly Rectifying - chemistry Potassium Channels, Inwardly Rectifying - genetics Potassium Channels, Inwardly Rectifying - metabolism Protein Structure, Tertiary - physiology Rats Receptors, Drug - chemistry Receptors, Drug - genetics Receptors, Drug - metabolism Sulfonylurea Receptors |
| title | cAMP-dependent Protein Kinase Phosphorylation Produces Interdomain Movement in SUR2B Leading to Activation of the Vascular KATP Channel |
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