Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments
The occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684–726 of the amyloid precursor protein APP reconstitut...
Gespeichert in:
| Veröffentlicht in: | Biophysical journal 2008-08, Vol.95 (3), p.1460-1473 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1473 |
|---|---|
| container_issue | 3 |
| container_start_page | 1460 |
| container_title | Biophysical journal |
| container_volume | 95 |
| creator | Marenchino, Marco Williamson, Philip T.F. Murri, Samuel Zandomeneghi, Giorgia Wunderli-Allenspach, Heidi Meier, Beat H. Krämer, Stefanie D. |
| description | The occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684–726 of the amyloid precursor protein APP reconstituted in liposomes. Solid-state NMR with
2H-Ala
713, which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (PhC) membranes than in dimyristoyl-phosphatidylcholine (DMPC) bilayers above the main phase transition temperature
T
c. The residue
15N-Ala
692, which is in the vicinity of the
α-cleavage site, i.e., Lys
687, showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomes <
T
c than in PhC, DMPC, or sphingomyelin vesicles. In all tested liposomal systems the
α-cleavage site was accessible for hydrolysis by trypsin. However, the catalytic rate constant was higher in the PhC and DMPC than in the sphingomyelin and distearoyl-phosphatidylcholine systems. In conclusion, the dynamics of APP(684–726) on the transmembrane level as well as the motion of the
α-cleavage site and its hydrolysis by a model enzyme are dependent on the bilayer characteristics. This could be relevant for the processing of APP in vivo. |
| doi_str_mv | 10.1529/biophysj.108.129726 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2479613</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006349508702133</els_id><sourcerecordid>69327521</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-6371452b2b9a43055947dd6b85cd5db2c5358e855294f75cb8706c5ceef23a6f3</originalsourceid><addsrcrecordid>eNp9kc1q3DAUhUVpaSZpn6BQtCrJwlP921o0ECbpDww00HYtZOk6o2DLU8kzMI_VF-kzVcHTv01WgqPvnqOrg9ArSpZUMv22DeN2c8j3S0qaJWW6ZuoJWlApWEVIo56iBSFEVVxoeYJOc74nhDJJ6HN0QhuuidR6gez1IdohuIxt9HjVg93bNvRhOmA74WkD-OePapbvAH8JE-Cxw1e3t-eqEVWJvMAh4uvQdZAgTngdtsHjm7gPaYxDUfIL9KyzfYaXx_MMfXt_83X1sVp__vBpdbWunNBkqhSvqZCsZa22ghMptai9V20jnZe-ZU5y2UAjy-aiq6Vrm5ooJx1Ax7hVHT9Dl7PvdtcO4F3JTrY32xQGmw5mtMH8fxPDxtyNe8NErRXlxeDN0SCN33eQJzOE7KDvbYRxl43SnNWS0QKePwrSWjFKOeEPnnxGXRpzTtD9eQ8l5qFF87vFIjRmbrFMvf53lb8zx9oK8G4GoHzoPkAy2QWIDnxI4Cbjx_BowC-DQq-S</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1762113033</pqid></control><display><type>article</type><title>Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>PubMed (Medline)</source><source>Cell Press Archives</source><source>EZB Electronic Journals Library</source><creator>Marenchino, Marco ; Williamson, Philip T.F. ; Murri, Samuel ; Zandomeneghi, Giorgia ; Wunderli-Allenspach, Heidi ; Meier, Beat H. ; Krämer, Stefanie D.</creator><creatorcontrib>Marenchino, Marco ; Williamson, Philip T.F. ; Murri, Samuel ; Zandomeneghi, Giorgia ; Wunderli-Allenspach, Heidi ; Meier, Beat H. ; Krämer, Stefanie D.</creatorcontrib><description>The occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684–726 of the amyloid precursor protein APP reconstituted in liposomes. Solid-state NMR with
2H-Ala
713, which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (PhC) membranes than in dimyristoyl-phosphatidylcholine (DMPC) bilayers above the main phase transition temperature
T
c. The residue
15N-Ala
692, which is in the vicinity of the
α-cleavage site, i.e., Lys
687, showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomes <
T
c than in PhC, DMPC, or sphingomyelin vesicles. In all tested liposomal systems the
α-cleavage site was accessible for hydrolysis by trypsin. However, the catalytic rate constant was higher in the PhC and DMPC than in the sphingomyelin and distearoyl-phosphatidylcholine systems. In conclusion, the dynamics of APP(684–726) on the transmembrane level as well as the motion of the
α-cleavage site and its hydrolysis by a model enzyme are dependent on the bilayer characteristics. This could be relevant for the processing of APP in vivo.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1529/biophysj.108.129726</identifier><identifier>PMID: 18390599</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amyloid beta-Protein Precursor - chemistry ; Binding Sites ; Cell Biophysics ; Computer Simulation ; Dynamical systems ; Dynamics ; Enzymes ; Hydrolysis ; Lipids ; Liposomes ; Liposomes - chemistry ; Membrane Lipids - chemistry ; Membranes ; Models, Chemical ; Models, Molecular ; Peptides ; Protein Binding</subject><ispartof>Biophysical journal, 2008-08, Vol.95 (3), p.1460-1473</ispartof><rights>2008 The Biophysical Society</rights><rights>Copyright © 2008, Biophysical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-6371452b2b9a43055947dd6b85cd5db2c5358e855294f75cb8706c5ceef23a6f3</citedby><cites>FETCH-LOGICAL-c490t-6371452b2b9a43055947dd6b85cd5db2c5358e855294f75cb8706c5ceef23a6f3</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/PMC2479613/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1529/biophysj.108.129726$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18390599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marenchino, Marco</creatorcontrib><creatorcontrib>Williamson, Philip T.F.</creatorcontrib><creatorcontrib>Murri, Samuel</creatorcontrib><creatorcontrib>Zandomeneghi, Giorgia</creatorcontrib><creatorcontrib>Wunderli-Allenspach, Heidi</creatorcontrib><creatorcontrib>Meier, Beat H.</creatorcontrib><creatorcontrib>Krämer, Stefanie D.</creatorcontrib><title>Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>The occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684–726 of the amyloid precursor protein APP reconstituted in liposomes. Solid-state NMR with
2H-Ala
713, which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (PhC) membranes than in dimyristoyl-phosphatidylcholine (DMPC) bilayers above the main phase transition temperature
T
c. The residue
15N-Ala
692, which is in the vicinity of the
α-cleavage site, i.e., Lys
687, showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomes <
T
c than in PhC, DMPC, or sphingomyelin vesicles. In all tested liposomal systems the
α-cleavage site was accessible for hydrolysis by trypsin. However, the catalytic rate constant was higher in the PhC and DMPC than in the sphingomyelin and distearoyl-phosphatidylcholine systems. In conclusion, the dynamics of APP(684–726) on the transmembrane level as well as the motion of the
α-cleavage site and its hydrolysis by a model enzyme are dependent on the bilayer characteristics. This could be relevant for the processing of APP in vivo.</description><subject>Amyloid beta-Protein Precursor - chemistry</subject><subject>Binding Sites</subject><subject>Cell Biophysics</subject><subject>Computer Simulation</subject><subject>Dynamical systems</subject><subject>Dynamics</subject><subject>Enzymes</subject><subject>Hydrolysis</subject><subject>Lipids</subject><subject>Liposomes</subject><subject>Liposomes - chemistry</subject><subject>Membrane Lipids - chemistry</subject><subject>Membranes</subject><subject>Models, Chemical</subject><subject>Models, Molecular</subject><subject>Peptides</subject><subject>Protein Binding</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1q3DAUhUVpaSZpn6BQtCrJwlP921o0ECbpDww00HYtZOk6o2DLU8kzMI_VF-kzVcHTv01WgqPvnqOrg9ArSpZUMv22DeN2c8j3S0qaJWW6ZuoJWlApWEVIo56iBSFEVVxoeYJOc74nhDJJ6HN0QhuuidR6gez1IdohuIxt9HjVg93bNvRhOmA74WkD-OePapbvAH8JE-Cxw1e3t-eqEVWJvMAh4uvQdZAgTngdtsHjm7gPaYxDUfIL9KyzfYaXx_MMfXt_83X1sVp__vBpdbWunNBkqhSvqZCsZa22ghMptai9V20jnZe-ZU5y2UAjy-aiq6Vrm5ooJx1Ax7hVHT9Dl7PvdtcO4F3JTrY32xQGmw5mtMH8fxPDxtyNe8NErRXlxeDN0SCN33eQJzOE7KDvbYRxl43SnNWS0QKePwrSWjFKOeEPnnxGXRpzTtD9eQ8l5qFF87vFIjRmbrFMvf53lb8zx9oK8G4GoHzoPkAy2QWIDnxI4Cbjx_BowC-DQq-S</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Marenchino, Marco</creator><creator>Williamson, Philip T.F.</creator><creator>Murri, Samuel</creator><creator>Zandomeneghi, Giorgia</creator><creator>Wunderli-Allenspach, Heidi</creator><creator>Meier, Beat H.</creator><creator>Krämer, Stefanie D.</creator><general>Elsevier Inc</general><general>The Biophysical Society</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>7TB</scope><scope>7U5</scope><scope>8FD</scope><scope>FR3</scope><scope>L7M</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080801</creationdate><title>Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments</title><author>Marenchino, Marco ; Williamson, Philip T.F. ; Murri, Samuel ; Zandomeneghi, Giorgia ; Wunderli-Allenspach, Heidi ; Meier, Beat H. ; Krämer, Stefanie D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-6371452b2b9a43055947dd6b85cd5db2c5358e855294f75cb8706c5ceef23a6f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Amyloid beta-Protein Precursor - chemistry</topic><topic>Binding Sites</topic><topic>Cell Biophysics</topic><topic>Computer Simulation</topic><topic>Dynamical systems</topic><topic>Dynamics</topic><topic>Enzymes</topic><topic>Hydrolysis</topic><topic>Lipids</topic><topic>Liposomes</topic><topic>Liposomes - chemistry</topic><topic>Membrane Lipids - chemistry</topic><topic>Membranes</topic><topic>Models, Chemical</topic><topic>Models, Molecular</topic><topic>Peptides</topic><topic>Protein Binding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marenchino, Marco</creatorcontrib><creatorcontrib>Williamson, Philip T.F.</creatorcontrib><creatorcontrib>Murri, Samuel</creatorcontrib><creatorcontrib>Zandomeneghi, Giorgia</creatorcontrib><creatorcontrib>Wunderli-Allenspach, Heidi</creatorcontrib><creatorcontrib>Meier, Beat H.</creatorcontrib><creatorcontrib>Krämer, Stefanie D.</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>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marenchino, Marco</au><au>Williamson, Philip T.F.</au><au>Murri, Samuel</au><au>Zandomeneghi, Giorgia</au><au>Wunderli-Allenspach, Heidi</au><au>Meier, Beat H.</au><au>Krämer, Stefanie D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>95</volume><issue>3</issue><spage>1460</spage><epage>1473</epage><pages>1460-1473</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>The occurrence of late-onset Alzheimer's disease has been related to the lipid homeostasis. We tested whether the membrane lipid environment affects the dynamics and cleavability of a model peptide corresponding to the amino acid sequence 684–726 of the amyloid precursor protein APP reconstituted in liposomes. Solid-state NMR with
2H-Ala
713, which is located within the putative transmembrane domain, suggested that the peptide observes less rotational motion in egg phosphatidylcholine (PhC) membranes than in dimyristoyl-phosphatidylcholine (DMPC) bilayers above the main phase transition temperature
T
c. The residue
15N-Ala
692, which is in the vicinity of the
α-cleavage site, i.e., Lys
687, showed less motion after reconstitution in distearoyl-phosphatidylcholine liposomes <
T
c than in PhC, DMPC, or sphingomyelin vesicles. In all tested liposomal systems the
α-cleavage site was accessible for hydrolysis by trypsin. However, the catalytic rate constant was higher in the PhC and DMPC than in the sphingomyelin and distearoyl-phosphatidylcholine systems. In conclusion, the dynamics of APP(684–726) on the transmembrane level as well as the motion of the
α-cleavage site and its hydrolysis by a model enzyme are dependent on the bilayer characteristics. This could be relevant for the processing of APP in vivo.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18390599</pmid><doi>10.1529/biophysj.108.129726</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-3495 |
| ispartof | Biophysical journal, 2008-08, Vol.95 (3), p.1460-1473 |
| issn | 0006-3495 1542-0086 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2479613 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete; PubMed (Medline); Cell Press Archives; EZB Electronic Journals Library |
| subjects | Amyloid beta-Protein Precursor - chemistry Binding Sites Cell Biophysics Computer Simulation Dynamical systems Dynamics Enzymes Hydrolysis Lipids Liposomes Liposomes - chemistry Membrane Lipids - chemistry Membranes Models, Chemical Models, Molecular Peptides Protein Binding |
| title | Dynamics and Cleavability at the α-Cleavage Site of APP(684-726) in Different Lipid Environments |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T00%3A03%3A48IST&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=Dynamics%20and%20Cleavability%20at%20the%20%CE%B1-Cleavage%20Site%20of%20APP(684-726)%20in%20Different%20Lipid%20Environments&rft.jtitle=Biophysical%20journal&rft.au=Marenchino,%20Marco&rft.date=2008-08-01&rft.volume=95&rft.issue=3&rft.spage=1460&rft.epage=1473&rft.pages=1460-1473&rft.issn=0006-3495&rft.eissn=1542-0086&rft_id=info:doi/10.1529/biophysj.108.129726&rft_dat=%3Cproquest_pubme%3E69327521%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=1762113033&rft_id=info:pmid/18390599&rft_els_id=S0006349508702133&rfr_iscdi=true |