Crystal Structures of β-Neurexin 1 and β-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4
Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca2+-dependent complexes that bridge neural synapses. β-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Δ. We present crystal s...
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| Veröffentlicht in: | Structure 2008-03, Vol.16 (3), p.410-421 |
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| creator | Koehnke, Jesko Jin, Xiangshu Trbovic, Nikola Katsamba, Phinikoula S. Brasch, Julia Ahlsen, Goran Scheiffele, Peter Honig, Barry Palmer, Arthur G. Shapiro, Lawrence |
| description | Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca2+-dependent complexes that bridge neural synapses. β-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Δ. We present crystal structures of the Δ isoforms of the LNS domains from β-NRX1 and β-NRX2, crystallized in the presence of Ca2+ ions. The Ca2+-binding site is disordered in the β-NRX2 structure, but the 1.7 Å β-NRX1 structure reveals a single Ca2+ ion, ∼12 Å from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent β-NRX1 molecule. NMR studies of β-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that β-NRX insertion sequence 4 may function in roles independent of neuroligin binding. |
| doi_str_mv | 10.1016/j.str.2007.12.024 |
| format | Article |
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We present crystal structures of the Δ isoforms of the LNS domains from β-NRX1 and β-NRX2, crystallized in the presence of Ca2+ ions. The Ca2+-binding site is disordered in the β-NRX2 structure, but the 1.7 Å β-NRX1 structure reveals a single Ca2+ ion, ∼12 Å from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent β-NRX1 molecule. NMR studies of β-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that β-NRX insertion sequence 4 may function in roles independent of neuroligin binding.</description><identifier>ISSN: 0969-2126</identifier><identifier>EISSN: 1878-4186</identifier><identifier>DOI: 10.1016/j.str.2007.12.024</identifier><identifier>PMID: 18334216</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>04 OIL SHALES AND TAR SANDS ; Amino Acid Sequence ; Animals ; BASIC BIOLOGICAL SCIENCES ; Binding ; Bridges (structures) ; CALCIUM ; Calcium - metabolism ; Cell Adhesion Molecules, Neuronal ; COMPLEXES ; CRYSTAL STRUCTURE ; Crystallography, X-Ray ; DYNAMICS ; FUNCTIONS ; GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE ; GLUTAMIC ACID ; Insertion ; IONS ; Joints ; LIGANDS ; MATERIALS SCIENCE ; Membrane Proteins - metabolism ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; national synchrotron light source ; Nerve Tissue Proteins - chemistry ; Nerve Tissue Proteins - metabolism ; NUCLEAR MAGNETIC RESONANCE ; Protein Binding ; Protein Isoforms - chemistry ; Protein Structure, Tertiary ; PROTEINS ; Rats ; Recombinant Proteins - chemistry ; RISE ; RNA Splice Sites ; Sequence Homology, Amino Acid ; SIGNALING ; SPLICING</subject><ispartof>Structure, 2008-03, Vol.16 (3), p.410-421</ispartof><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-6108dd35b71c699d111072966bdfae2c172114e6eba2c226d09ec49d3a182d8f3</citedby><cites>FETCH-LOGICAL-c508t-6108dd35b71c699d111072966bdfae2c172114e6eba2c226d09ec49d3a182d8f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.str.2007.12.024$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18334216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/980111$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Koehnke, Jesko</creatorcontrib><creatorcontrib>Jin, Xiangshu</creatorcontrib><creatorcontrib>Trbovic, Nikola</creatorcontrib><creatorcontrib>Katsamba, Phinikoula S.</creatorcontrib><creatorcontrib>Brasch, Julia</creatorcontrib><creatorcontrib>Ahlsen, Goran</creatorcontrib><creatorcontrib>Scheiffele, Peter</creatorcontrib><creatorcontrib>Honig, Barry</creatorcontrib><creatorcontrib>Palmer, Arthur G.</creatorcontrib><creatorcontrib>Shapiro, Lawrence</creatorcontrib><creatorcontrib>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</creatorcontrib><title>Crystal Structures of β-Neurexin 1 and β-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4</title><title>Structure</title><addtitle>Structure</addtitle><description>Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca2+-dependent complexes that bridge neural synapses. β-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Δ. We present crystal structures of the Δ isoforms of the LNS domains from β-NRX1 and β-NRX2, crystallized in the presence of Ca2+ ions. The Ca2+-binding site is disordered in the β-NRX2 structure, but the 1.7 Å β-NRX1 structure reveals a single Ca2+ ion, ∼12 Å from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent β-NRX1 molecule. NMR studies of β-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that β-NRX insertion sequence 4 may function in roles independent of neuroligin binding.</description><subject>04 OIL SHALES AND TAR SANDS</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Binding</subject><subject>Bridges (structures)</subject><subject>CALCIUM</subject><subject>Calcium - metabolism</subject><subject>Cell Adhesion Molecules, Neuronal</subject><subject>COMPLEXES</subject><subject>CRYSTAL STRUCTURE</subject><subject>Crystallography, X-Ray</subject><subject>DYNAMICS</subject><subject>FUNCTIONS</subject><subject>GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE</subject><subject>GLUTAMIC ACID</subject><subject>Insertion</subject><subject>IONS</subject><subject>Joints</subject><subject>LIGANDS</subject><subject>MATERIALS SCIENCE</subject><subject>Membrane Proteins - metabolism</subject><subject>Models, Biological</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>national synchrotron light source</subject><subject>Nerve Tissue Proteins - chemistry</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>NUCLEAR MAGNETIC RESONANCE</subject><subject>Protein Binding</subject><subject>Protein Isoforms - chemistry</subject><subject>Protein Structure, Tertiary</subject><subject>PROTEINS</subject><subject>Rats</subject><subject>Recombinant Proteins - chemistry</subject><subject>RISE</subject><subject>RNA Splice Sites</subject><subject>Sequence Homology, Amino Acid</subject><subject>SIGNALING</subject><subject>SPLICING</subject><issn>0969-2126</issn><issn>1878-4186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhiMEokvhAbigcEG9JHjGWccRUiW0LVCpgsPC2fLaDvUqsRfbqdjX4kF4JpzuCuilJ8sz3_ye339RvARSAwH2dlvHFGokpK0Ba4LNo2IBvOVVA5w9LhakY12FgOykeBbjlhCCS0KeFifAKW0Q2KIYV2EfkxzKdQqTSlMwsfR9-ftX9dnky0_rSiil0_cqWF6q5LUfpXXxrnuxd3K06m52vRusMuWViyYk6125Nj8m43KpeV486eUQzYvjeVp8-3D5dfWpuv7y8Wr1_rpSS8JTxYBwrely04JiXacBgLTYMbbRvTSooEWAxjCzkagQmSadUU2nqQSOmvf0tDg_6O6mzWi0Mi4FOYhdsKMMe-GlFfc7zt6I7_5WYJsXYMss8Pog4GOyIiqbjLpR3jmjkug4yRtl5s3xkeCzwZjEaKMywyCd8VMULaEdciQZPHsQBNYCUkoJzSgcUBV8jMH0f3cGIubMxVbkzMWcuQAUOfM88-p_s_8mjiFn4N0BMPnLb60Js6E5EG3D7Ed7-4D8HxRLvj8</recordid><startdate>20080301</startdate><enddate>20080301</enddate><creator>Koehnke, Jesko</creator><creator>Jin, Xiangshu</creator><creator>Trbovic, Nikola</creator><creator>Katsamba, Phinikoula S.</creator><creator>Brasch, Julia</creator><creator>Ahlsen, Goran</creator><creator>Scheiffele, Peter</creator><creator>Honig, Barry</creator><creator>Palmer, Arthur G.</creator><creator>Shapiro, Lawrence</creator><general>Elsevier Inc</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>7U5</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>L7M</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20080301</creationdate><title>Crystal Structures of β-Neurexin 1 and β-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4</title><author>Koehnke, Jesko ; 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We present crystal structures of the Δ isoforms of the LNS domains from β-NRX1 and β-NRX2, crystallized in the presence of Ca2+ ions. The Ca2+-binding site is disordered in the β-NRX2 structure, but the 1.7 Å β-NRX1 structure reveals a single Ca2+ ion, ∼12 Å from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent β-NRX1 molecule. NMR studies of β-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that β-NRX insertion sequence 4 may function in roles independent of neuroligin binding.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18334216</pmid><doi>10.1016/j.str.2007.12.024</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 04 OIL SHALES AND TAR SANDS Amino Acid Sequence Animals BASIC BIOLOGICAL SCIENCES Binding Bridges (structures) CALCIUM Calcium - metabolism Cell Adhesion Molecules, Neuronal COMPLEXES CRYSTAL STRUCTURE Crystallography, X-Ray DYNAMICS FUNCTIONS GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE GLUTAMIC ACID Insertion IONS Joints LIGANDS MATERIALS SCIENCE Membrane Proteins - metabolism Models, Biological Models, Molecular Molecular Sequence Data national synchrotron light source Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - metabolism NUCLEAR MAGNETIC RESONANCE Protein Binding Protein Isoforms - chemistry Protein Structure, Tertiary PROTEINS Rats Recombinant Proteins - chemistry RISE RNA Splice Sites Sequence Homology, Amino Acid SIGNALING SPLICING |
| title | Crystal Structures of β-Neurexin 1 and β-Neurexin 2 Ectodomains and Dynamics of Splice Insertion Sequence 4 |
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