The FKBP-Type Domain of the Human Aryl Hydrocarbon Receptor-Interacting Protein Reveals an Unusual Hsp90 Interaction
The aryl hydrocarbon receptor-interacting protein (AIP) has been predicted to consist of an N-terminal FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) domain and a C-terminal tetratricopeptide repeat (TPR) domain, as typically found in FK506-binding immunophilins. AIP, however, exhibited no i...
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Veröffentlicht in: | Biochemistry (Easton) 2013-03, Vol.52 (12), p.2097-2107 |
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creator | Linnert, Miriam Lin, Yi-Jan Manns, Annika Haupt, Katja Paschke, Anne-Katrin Fischer, Gunter Weiwad, Matthias Lücke, Christian |
description | The aryl hydrocarbon receptor-interacting protein (AIP) has been predicted to consist of an N-terminal FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) domain and a C-terminal tetratricopeptide repeat (TPR) domain, as typically found in FK506-binding immunophilins. AIP, however, exhibited no inherent FK506 binding or PPIase activity. Alignment with the prototypic FKBP12 showed a high sequence homology but indicated inconsistencies with regard to the secondary structure prediction derived from chemical shift analysis of AIP2–166. NMR-based structure determination of AIP2–166 now revealed a typical FKBP fold with five antiparallel β-strands forming a half β-barrel wrapped around a central α-helix, thus permitting AIP to be also named FKBP37.7 according to FKBP nomenclature. This PPIase domain, however, features two structure elements that are unusual for FKBPs: (i) an N-terminal α-helix, which additionally stabilizes the domain, and (ii) a rather long insert, which connects the last two β-strands and covers the putative active site. Diminution of the latter insert did not generate PPIase activity or FK506 binding capability, indicating that the lack of catalytic activity in AIP is the result of structural differences within the PPIase domain. Compared to active FKBPs, a diverging conformation of the loop connecting β-strand C′ and the central α-helix apparently is responsible for this inherent lack of catalytic activity in AIP. Moreover, Hsp90 was identified as potential physiological interaction partner of AIP, which revealed binding contacts not only at the TPR domain but uncommonly also at the PPIase domain. |
doi_str_mv | 10.1021/bi301649m |
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AIP, however, exhibited no inherent FK506 binding or PPIase activity. Alignment with the prototypic FKBP12 showed a high sequence homology but indicated inconsistencies with regard to the secondary structure prediction derived from chemical shift analysis of AIP2–166. NMR-based structure determination of AIP2–166 now revealed a typical FKBP fold with five antiparallel β-strands forming a half β-barrel wrapped around a central α-helix, thus permitting AIP to be also named FKBP37.7 according to FKBP nomenclature. This PPIase domain, however, features two structure elements that are unusual for FKBPs: (i) an N-terminal α-helix, which additionally stabilizes the domain, and (ii) a rather long insert, which connects the last two β-strands and covers the putative active site. Diminution of the latter insert did not generate PPIase activity or FK506 binding capability, indicating that the lack of catalytic activity in AIP is the result of structural differences within the PPIase domain. Compared to active FKBPs, a diverging conformation of the loop connecting β-strand C′ and the central α-helix apparently is responsible for this inherent lack of catalytic activity in AIP. Moreover, Hsp90 was identified as potential physiological interaction partner of AIP, which revealed binding contacts not only at the TPR domain but uncommonly also at the PPIase domain.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi301649m</identifier><identifier>PMID: 23418784</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amino Acid Sequence ; HSP90 Heat-Shock Proteins - chemistry ; HSP90 Heat-Shock Proteins - metabolism ; Humans ; Intracellular Signaling Peptides and Proteins - chemistry ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Peptidylprolyl Isomerase - chemistry ; Peptidylprolyl Isomerase - genetics ; Peptidylprolyl Isomerase - metabolism ; Protein Conformation ; Protein Interaction Domains and Motifs ; Sequence Homology, Amino Acid ; Structural Homology, Protein ; Tacrolimus - metabolism ; Tacrolimus Binding Protein 1A - chemistry ; Tacrolimus Binding Protein 1A - genetics ; Tacrolimus Binding Protein 1A - metabolism ; Tacrolimus Binding Proteins - chemistry ; Tacrolimus Binding Proteins - genetics ; Tacrolimus Binding Proteins - metabolism</subject><ispartof>Biochemistry (Easton), 2013-03, Vol.52 (12), p.2097-2107</ispartof><rights>Copyright © 2013 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-62de604ab7ffd3c7dc137df7cc6f1026bcde19e8127917abdd80fb9df7169f653</citedby><cites>FETCH-LOGICAL-a315t-62de604ab7ffd3c7dc137df7cc6f1026bcde19e8127917abdd80fb9df7169f653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi301649m$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi301649m$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23418784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Linnert, Miriam</creatorcontrib><creatorcontrib>Lin, Yi-Jan</creatorcontrib><creatorcontrib>Manns, Annika</creatorcontrib><creatorcontrib>Haupt, Katja</creatorcontrib><creatorcontrib>Paschke, Anne-Katrin</creatorcontrib><creatorcontrib>Fischer, Gunter</creatorcontrib><creatorcontrib>Weiwad, Matthias</creatorcontrib><creatorcontrib>Lücke, Christian</creatorcontrib><title>The FKBP-Type Domain of the Human Aryl Hydrocarbon Receptor-Interacting Protein Reveals an Unusual Hsp90 Interaction</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>The aryl hydrocarbon receptor-interacting protein (AIP) has been predicted to consist of an N-terminal FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) domain and a C-terminal tetratricopeptide repeat (TPR) domain, as typically found in FK506-binding immunophilins. AIP, however, exhibited no inherent FK506 binding or PPIase activity. Alignment with the prototypic FKBP12 showed a high sequence homology but indicated inconsistencies with regard to the secondary structure prediction derived from chemical shift analysis of AIP2–166. NMR-based structure determination of AIP2–166 now revealed a typical FKBP fold with five antiparallel β-strands forming a half β-barrel wrapped around a central α-helix, thus permitting AIP to be also named FKBP37.7 according to FKBP nomenclature. This PPIase domain, however, features two structure elements that are unusual for FKBPs: (i) an N-terminal α-helix, which additionally stabilizes the domain, and (ii) a rather long insert, which connects the last two β-strands and covers the putative active site. Diminution of the latter insert did not generate PPIase activity or FK506 binding capability, indicating that the lack of catalytic activity in AIP is the result of structural differences within the PPIase domain. Compared to active FKBPs, a diverging conformation of the loop connecting β-strand C′ and the central α-helix apparently is responsible for this inherent lack of catalytic activity in AIP. Moreover, Hsp90 was identified as potential physiological interaction partner of AIP, which revealed binding contacts not only at the TPR domain but uncommonly also at the PPIase domain.</description><subject>Amino Acid Sequence</subject><subject>HSP90 Heat-Shock Proteins - chemistry</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - chemistry</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Peptidylprolyl Isomerase - chemistry</subject><subject>Peptidylprolyl Isomerase - genetics</subject><subject>Peptidylprolyl Isomerase - metabolism</subject><subject>Protein Conformation</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Sequence Homology, Amino Acid</subject><subject>Structural Homology, Protein</subject><subject>Tacrolimus - metabolism</subject><subject>Tacrolimus Binding Protein 1A - chemistry</subject><subject>Tacrolimus Binding Protein 1A - genetics</subject><subject>Tacrolimus Binding Protein 1A - metabolism</subject><subject>Tacrolimus Binding Proteins - chemistry</subject><subject>Tacrolimus Binding Proteins - genetics</subject><subject>Tacrolimus Binding Proteins - metabolism</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1LwzAYB_AgipvTg19AchH0UE36kjbHOZ0bDhyynUuaF-1Yk5qkQr-9GZs7eQpJfs8fnj8A1xg9YBTjx6pOECYpbU7AEGcxilJKs1MwRAiRKKYEDcCFc5twTVGenoNBnKS4yIt0CPzqS8Lp29MyWvWthM-mYbWGRkEf3mddwzQc234LZ72whjNbGQ0_JJetNzaaay8t477Wn3BpjZf17vNHsq2DYXCtO9exMOtaiuARG30JzlQw8upwjsB6-rKazKLF--t8Ml5ELMGZj0gsJEEpq3KlRMJzwXGSC5VzTlTYm1RcSExlgeOc4pxVQhRIVTQITKgiWTICd_vc1prvTjpfNrXjcrtlWprOlTglWUFIRmig93vKrXHOSlW2tm6Y7UuMyl3J5bHkYG8OsV3VSHGUf60GcLsHjLtyYzqrw5b_BP0CLgiDzw</recordid><startdate>20130326</startdate><enddate>20130326</enddate><creator>Linnert, Miriam</creator><creator>Lin, Yi-Jan</creator><creator>Manns, Annika</creator><creator>Haupt, Katja</creator><creator>Paschke, Anne-Katrin</creator><creator>Fischer, Gunter</creator><creator>Weiwad, Matthias</creator><creator>Lücke, Christian</creator><general>American Chemical Society</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>7X8</scope></search><sort><creationdate>20130326</creationdate><title>The FKBP-Type Domain of the Human Aryl Hydrocarbon Receptor-Interacting Protein Reveals an Unusual Hsp90 Interaction</title><author>Linnert, Miriam ; Lin, Yi-Jan ; Manns, Annika ; Haupt, Katja ; Paschke, Anne-Katrin ; Fischer, Gunter ; Weiwad, Matthias ; Lücke, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-62de604ab7ffd3c7dc137df7cc6f1026bcde19e8127917abdd80fb9df7169f653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Sequence</topic><topic>HSP90 Heat-Shock Proteins - chemistry</topic><topic>HSP90 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - chemistry</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Peptidylprolyl Isomerase - chemistry</topic><topic>Peptidylprolyl Isomerase - genetics</topic><topic>Peptidylprolyl Isomerase - metabolism</topic><topic>Protein Conformation</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Sequence Homology, Amino Acid</topic><topic>Structural Homology, Protein</topic><topic>Tacrolimus - metabolism</topic><topic>Tacrolimus Binding Protein 1A - chemistry</topic><topic>Tacrolimus Binding Protein 1A - genetics</topic><topic>Tacrolimus Binding Protein 1A - metabolism</topic><topic>Tacrolimus Binding Proteins - chemistry</topic><topic>Tacrolimus Binding Proteins - genetics</topic><topic>Tacrolimus Binding Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Linnert, Miriam</creatorcontrib><creatorcontrib>Lin, Yi-Jan</creatorcontrib><creatorcontrib>Manns, Annika</creatorcontrib><creatorcontrib>Haupt, Katja</creatorcontrib><creatorcontrib>Paschke, Anne-Katrin</creatorcontrib><creatorcontrib>Fischer, Gunter</creatorcontrib><creatorcontrib>Weiwad, Matthias</creatorcontrib><creatorcontrib>Lücke, Christian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Linnert, Miriam</au><au>Lin, Yi-Jan</au><au>Manns, Annika</au><au>Haupt, Katja</au><au>Paschke, Anne-Katrin</au><au>Fischer, Gunter</au><au>Weiwad, Matthias</au><au>Lücke, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The FKBP-Type Domain of the Human Aryl Hydrocarbon Receptor-Interacting Protein Reveals an Unusual Hsp90 Interaction</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>2013-03-26</date><risdate>2013</risdate><volume>52</volume><issue>12</issue><spage>2097</spage><epage>2107</epage><pages>2097-2107</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>The aryl hydrocarbon receptor-interacting protein (AIP) has been predicted to consist of an N-terminal FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) domain and a C-terminal tetratricopeptide repeat (TPR) domain, as typically found in FK506-binding immunophilins. AIP, however, exhibited no inherent FK506 binding or PPIase activity. Alignment with the prototypic FKBP12 showed a high sequence homology but indicated inconsistencies with regard to the secondary structure prediction derived from chemical shift analysis of AIP2–166. NMR-based structure determination of AIP2–166 now revealed a typical FKBP fold with five antiparallel β-strands forming a half β-barrel wrapped around a central α-helix, thus permitting AIP to be also named FKBP37.7 according to FKBP nomenclature. This PPIase domain, however, features two structure elements that are unusual for FKBPs: (i) an N-terminal α-helix, which additionally stabilizes the domain, and (ii) a rather long insert, which connects the last two β-strands and covers the putative active site. Diminution of the latter insert did not generate PPIase activity or FK506 binding capability, indicating that the lack of catalytic activity in AIP is the result of structural differences within the PPIase domain. Compared to active FKBPs, a diverging conformation of the loop connecting β-strand C′ and the central α-helix apparently is responsible for this inherent lack of catalytic activity in AIP. Moreover, Hsp90 was identified as potential physiological interaction partner of AIP, which revealed binding contacts not only at the TPR domain but uncommonly also at the PPIase domain.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23418784</pmid><doi>10.1021/bi301649m</doi><tpages>11</tpages></addata></record> |
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subjects | Amino Acid Sequence HSP90 Heat-Shock Proteins - chemistry HSP90 Heat-Shock Proteins - metabolism Humans Intracellular Signaling Peptides and Proteins - chemistry Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Peptidylprolyl Isomerase - chemistry Peptidylprolyl Isomerase - genetics Peptidylprolyl Isomerase - metabolism Protein Conformation Protein Interaction Domains and Motifs Sequence Homology, Amino Acid Structural Homology, Protein Tacrolimus - metabolism Tacrolimus Binding Protein 1A - chemistry Tacrolimus Binding Protein 1A - genetics Tacrolimus Binding Protein 1A - metabolism Tacrolimus Binding Proteins - chemistry Tacrolimus Binding Proteins - genetics Tacrolimus Binding Proteins - metabolism |
title | The FKBP-Type Domain of the Human Aryl Hydrocarbon Receptor-Interacting Protein Reveals an Unusual Hsp90 Interaction |
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