The peroxisomal protein import machinery displays a preference for monomeric substrates
Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and transported by the shuttling receptor PEX5 to the peroxisomal membrane docking/translocation machinery, where they are translocated into the organelle matrix. Under certain experimental conditions this protein import machinery ha...
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description | Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and transported by the shuttling receptor PEX5 to the peroxisomal membrane docking/translocation machinery, where they are translocated into the organelle matrix. Under certain experimental conditions this protein import machinery has the remarkable capacity to accept already oligomerized proteins, a property that has heavily influenced current models on the mechanism of peroxisomal protein import. However, whether or not oligomeric proteins are really the best and most frequent clients of this machinery remain unclear. In this work, we present three lines of evidence suggesting that the peroxisomal import machinery displays a preference for monomeric proteins. First, in agreement with previous findings on catalase, we show that PEX5 binds newly synthesized (monomeric) acyl-CoA oxidase 1 (ACOX1) and urate oxidase (UOX), potently inhibiting their oligomerization. Second, in vitro import experiments suggest that monomeric ACOX1 and UOX are better peroxisomal import substrates than the corresponding oligomeric forms. Finally, we provide data strongly suggesting that although ACOX1 lacking a peroxisomal targeting signal can be imported into peroxisomes when co-expressed with ACOX1 containing its targeting signal, this import pathway is inefficient. |
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Under certain experimental conditions this protein import machinery has the remarkable capacity to accept already oligomerized proteins, a property that has heavily influenced current models on the mechanism of peroxisomal protein import. However, whether or not oligomeric proteins are really the best and most frequent clients of this machinery remain unclear. In this work, we present three lines of evidence suggesting that the peroxisomal import machinery displays a preference for monomeric proteins. First, in agreement with previous findings on catalase, we show that PEX5 binds newly synthesized (monomeric) acyl-CoA oxidase 1 (ACOX1) and urate oxidase (UOX), potently inhibiting their oligomerization. Second, in vitro import experiments suggest that monomeric ACOX1 and UOX are better peroxisomal import substrates than the corresponding oligomeric forms. Finally, we provide data strongly suggesting that although ACOX1 lacking a peroxisomal targeting signal can be imported into peroxisomes when co-expressed with ACOX1 containing its targeting signal, this import pathway is inefficient.</description><identifier>ISSN: 2046-2441</identifier><identifier>EISSN: 2046-2441</identifier><identifier>DOI: 10.1098/rsob.140236</identifier><identifier>PMID: 25854684</identifier><language>eng</language><publisher>England: The Royal Society</publisher><subject>Acyl-Coa Oxidase ; Acyl-CoA Oxidase - chemistry ; Acyl-CoA Oxidase - genetics ; Acyl-CoA Oxidase - metabolism ; Animals ; Blotting, Western ; Cercopithecus aethiops ; COS Cells ; Cytosol - metabolism ; Docking/translocation Machinery ; Humans ; Mice ; Microscopy, Fluorescence ; Models, Biological ; Mutation ; Peroxisome-Targeting Signal 1 Receptor ; Peroxisomes ; Peroxisomes - metabolism ; Pex5 ; Protein Binding ; Protein Import ; Protein Multimerization ; Protein Transport ; Rats ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; Signal Transduction ; Urate Oxidase ; Urate Oxidase - chemistry ; Urate Oxidase - genetics ; Urate Oxidase - metabolism</subject><ispartof>Open biology, 2015-04, Vol.5 (4), p.140236-140236</ispartof><rights>2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c599t-c2cfa14ef584b446f31b3f5603c3c92b509c0e00d4881a9eea44f67b518b4a0b3</citedby><cites>FETCH-LOGICAL-c599t-c2cfa14ef584b446f31b3f5603c3c92b509c0e00d4881a9eea44f67b518b4a0b3</cites><orcidid>0000-0001-5197-2270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422123/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422123/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,3322,27147,27924,27925,53791,53793,55555,55565</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25854684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freitas, Marta O.</creatorcontrib><creatorcontrib>Francisco, Tânia</creatorcontrib><creatorcontrib>Rodrigues, Tony A.</creatorcontrib><creatorcontrib>Lismont, Celien</creatorcontrib><creatorcontrib>Domingues, Pedro</creatorcontrib><creatorcontrib>Pinto, Manuel P.</creatorcontrib><creatorcontrib>Grou, Cláudia P.</creatorcontrib><creatorcontrib>Fransen, Marc</creatorcontrib><creatorcontrib>Azevedo, Jorge E.</creatorcontrib><title>The peroxisomal protein import machinery displays a preference for monomeric substrates</title><title>Open biology</title><addtitle>Open Biol</addtitle><addtitle>Open Biol</addtitle><description>Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and transported by the shuttling receptor PEX5 to the peroxisomal membrane docking/translocation machinery, where they are translocated into the organelle matrix. Under certain experimental conditions this protein import machinery has the remarkable capacity to accept already oligomerized proteins, a property that has heavily influenced current models on the mechanism of peroxisomal protein import. However, whether or not oligomeric proteins are really the best and most frequent clients of this machinery remain unclear. In this work, we present three lines of evidence suggesting that the peroxisomal import machinery displays a preference for monomeric proteins. First, in agreement with previous findings on catalase, we show that PEX5 binds newly synthesized (monomeric) acyl-CoA oxidase 1 (ACOX1) and urate oxidase (UOX), potently inhibiting their oligomerization. Second, in vitro import experiments suggest that monomeric ACOX1 and UOX are better peroxisomal import substrates than the corresponding oligomeric forms. Finally, we provide data strongly suggesting that although ACOX1 lacking a peroxisomal targeting signal can be imported into peroxisomes when co-expressed with ACOX1 containing its targeting signal, this import pathway is inefficient.</description><subject>Acyl-Coa Oxidase</subject><subject>Acyl-CoA Oxidase - chemistry</subject><subject>Acyl-CoA Oxidase - genetics</subject><subject>Acyl-CoA Oxidase - metabolism</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Cytosol - metabolism</subject><subject>Docking/translocation Machinery</subject><subject>Humans</subject><subject>Mice</subject><subject>Microscopy, Fluorescence</subject><subject>Models, Biological</subject><subject>Mutation</subject><subject>Peroxisome-Targeting Signal 1 Receptor</subject><subject>Peroxisomes</subject><subject>Peroxisomes - metabolism</subject><subject>Pex5</subject><subject>Protein Binding</subject><subject>Protein Import</subject><subject>Protein Multimerization</subject><subject>Protein Transport</subject><subject>Rats</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Signal Transduction</subject><subject>Urate Oxidase</subject><subject>Urate Oxidase - chemistry</subject><subject>Urate Oxidase - genetics</subject><subject>Urate Oxidase - metabolism</subject><issn>2046-2441</issn><issn>2046-2441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9kdFr1TAUxosobsw9-S59FOTOJD1JmxdBx9TBYKATH3wISXqym0vb1KQd1r_ezM5xJ2JekpN8_L6T8xXFc0pOKJHN65iCOaFAWCUeFYeMgNgwAPp473xQHKe0I3lxQSXQp8UB4w0H0cBh8fVqi-WIMfzwKfS6K8cYJvRD6fsxxKnstd36AeNStj6NnV5SqbMGHUYcLJYuxLIPQ-gxelum2aQp6gnTs-KJ013C47v9qPjy_uzq9OPm4vLD-enbi43lUk4by6zTFNDxBgyAcBU1leOCVLaykhlOpCVISAtNQ7VE1ABO1IbTxoAmpjoqzlduG_ROjdH3Oi4qaK9-X4R4rXScvO1Q8YoykmlSOg3SMG0Y53ULVhrnaOMy683KGmfTY2txyH_pHkAfvgx-q67DjQJgjLIqA17eAWL4PmOaVO-Txa7TA4Y5KSpqJkgta5alr1apjSGlPM97G0rUbbLqNlm1JpvVL_Y7u9f-yTELvq2CGJY87mA9TovahTkOuVSfPl--u-EeFGkqSoDXVKifflw9uPIpzahg3_Ive_I_-r86_gW5_dE_</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Freitas, Marta O.</creator><creator>Francisco, Tânia</creator><creator>Rodrigues, Tony A.</creator><creator>Lismont, Celien</creator><creator>Domingues, Pedro</creator><creator>Pinto, Manuel P.</creator><creator>Grou, Cláudia P.</creator><creator>Fransen, Marc</creator><creator>Azevedo, Jorge E.</creator><general>The Royal 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><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5197-2270</orcidid></search><sort><creationdate>20150401</creationdate><title>The peroxisomal protein import machinery displays a preference for monomeric substrates</title><author>Freitas, Marta O. ; Francisco, Tânia ; Rodrigues, Tony A. ; Lismont, Celien ; Domingues, Pedro ; Pinto, Manuel P. ; Grou, Cláudia P. ; Fransen, Marc ; Azevedo, Jorge E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c599t-c2cfa14ef584b446f31b3f5603c3c92b509c0e00d4881a9eea44f67b518b4a0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acyl-Coa Oxidase</topic><topic>Acyl-CoA Oxidase - chemistry</topic><topic>Acyl-CoA Oxidase - genetics</topic><topic>Acyl-CoA Oxidase - metabolism</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Cytosol - metabolism</topic><topic>Docking/translocation Machinery</topic><topic>Humans</topic><topic>Mice</topic><topic>Microscopy, Fluorescence</topic><topic>Models, Biological</topic><topic>Mutation</topic><topic>Peroxisome-Targeting Signal 1 Receptor</topic><topic>Peroxisomes</topic><topic>Peroxisomes - metabolism</topic><topic>Pex5</topic><topic>Protein Binding</topic><topic>Protein Import</topic><topic>Protein Multimerization</topic><topic>Protein Transport</topic><topic>Rats</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Signal Transduction</topic><topic>Urate Oxidase</topic><topic>Urate Oxidase - chemistry</topic><topic>Urate Oxidase - genetics</topic><topic>Urate Oxidase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freitas, Marta O.</creatorcontrib><creatorcontrib>Francisco, Tânia</creatorcontrib><creatorcontrib>Rodrigues, Tony A.</creatorcontrib><creatorcontrib>Lismont, Celien</creatorcontrib><creatorcontrib>Domingues, Pedro</creatorcontrib><creatorcontrib>Pinto, Manuel P.</creatorcontrib><creatorcontrib>Grou, Cláudia P.</creatorcontrib><creatorcontrib>Fransen, Marc</creatorcontrib><creatorcontrib>Azevedo, Jorge E.</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><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Open biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freitas, Marta O.</au><au>Francisco, Tânia</au><au>Rodrigues, Tony A.</au><au>Lismont, Celien</au><au>Domingues, Pedro</au><au>Pinto, Manuel P.</au><au>Grou, Cláudia P.</au><au>Fransen, Marc</au><au>Azevedo, Jorge E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The peroxisomal protein import machinery displays a preference for monomeric substrates</atitle><jtitle>Open biology</jtitle><stitle>Open Biol</stitle><addtitle>Open Biol</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>5</volume><issue>4</issue><spage>140236</spage><epage>140236</epage><pages>140236-140236</pages><issn>2046-2441</issn><eissn>2046-2441</eissn><abstract>Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and transported by the shuttling receptor PEX5 to the peroxisomal membrane docking/translocation machinery, where they are translocated into the organelle matrix. Under certain experimental conditions this protein import machinery has the remarkable capacity to accept already oligomerized proteins, a property that has heavily influenced current models on the mechanism of peroxisomal protein import. However, whether or not oligomeric proteins are really the best and most frequent clients of this machinery remain unclear. In this work, we present three lines of evidence suggesting that the peroxisomal import machinery displays a preference for monomeric proteins. First, in agreement with previous findings on catalase, we show that PEX5 binds newly synthesized (monomeric) acyl-CoA oxidase 1 (ACOX1) and urate oxidase (UOX), potently inhibiting their oligomerization. Second, in vitro import experiments suggest that monomeric ACOX1 and UOX are better peroxisomal import substrates than the corresponding oligomeric forms. Finally, we provide data strongly suggesting that although ACOX1 lacking a peroxisomal targeting signal can be imported into peroxisomes when co-expressed with ACOX1 containing its targeting signal, this import pathway is inefficient.</abstract><cop>England</cop><pub>The Royal Society</pub><pmid>25854684</pmid><doi>10.1098/rsob.140236</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5197-2270</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acyl-Coa Oxidase Acyl-CoA Oxidase - chemistry Acyl-CoA Oxidase - genetics Acyl-CoA Oxidase - metabolism Animals Blotting, Western Cercopithecus aethiops COS Cells Cytosol - metabolism Docking/translocation Machinery Humans Mice Microscopy, Fluorescence Models, Biological Mutation Peroxisome-Targeting Signal 1 Receptor Peroxisomes Peroxisomes - metabolism Pex5 Protein Binding Protein Import Protein Multimerization Protein Transport Rats Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Signal Transduction Urate Oxidase Urate Oxidase - chemistry Urate Oxidase - genetics Urate Oxidase - metabolism |
title | The peroxisomal protein import machinery displays a preference for monomeric substrates |
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