Structural insights into SUN-KASH complexes across the nuclear envelope
Linker of the nucleoskeleton and the cytoskeleton （LINC） complexes are composed of SUN and KASH domain- containing proteins and bridge the inner and outer membranes of the nuclear envelope. LINC complexes play criti- cal roles in nuclear positioning, cell polarization and cellular stiffness. Previou...
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| Veröffentlicht in: | Cell research 2012-10, Vol.22 (10), p.1440-1452 |
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| creator | Wang, Wenjia Shi, Zhubing Jiao, Shi Chen, Cuicui Wang, Huizhen Liu, Guoguang Wang, Qiang Zhao, Yun Greene, Mark I Zhou, Zhaocai |
| description | Linker of the nucleoskeleton and the cytoskeleton （LINC） complexes are composed of SUN and KASH domain- containing proteins and bridge the inner and outer membranes of the nuclear envelope. LINC complexes play criti- cal roles in nuclear positioning, cell polarization and cellular stiffness. Previously, we reported the homotrimeric structure of human SUN2. We have now determined the crystal structure of the human SUN2-KASH complex. In the complex structure, the SUN domain homotrimer binds to three independent ＂hook＂-like KASH peptides. The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state. A major conformational change involves the AA＇-loop of KASH-bound SUN domain, which rearranges to form a mini β-sheet that interacts with the KASH peptide. The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain, which we termed the BI-pocket. Moreover, two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding. Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro. In addition, transfection of wild-type, but not mutant, SUN2 promotes cell migration in Ovcar-3 cells. These results provide a structural model of the LINC complex, which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm. |
| doi_str_mv | 10.1038/cr.2012.126 |
| format | Article |
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LINC complexes play criti- cal roles in nuclear positioning, cell polarization and cellular stiffness. Previously, we reported the homotrimeric structure of human SUN2. We have now determined the crystal structure of the human SUN2-KASH complex. In the complex structure, the SUN domain homotrimer binds to three independent ＂hook＂-like KASH peptides. The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state. A major conformational change involves the AA＇-loop of KASH-bound SUN domain, which rearranges to form a mini β-sheet that interacts with the KASH peptide. The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain, which we termed the BI-pocket. Moreover, two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding. Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro. In addition, transfection of wild-type, but not mutant, SUN2 promotes cell migration in Ovcar-3 cells. These results provide a structural model of the LINC complex, which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.</description><identifier>ISSN: 1001-0602</identifier><identifier>EISSN: 1748-7838</identifier><identifier>DOI: 10.1038/cr.2012.126</identifier><identifier>PMID: 22945352</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/535 ; Amino Acid Motifs ; Binding Sites ; Biomedical and Life Sciences ; Cell Biology ; Cell Line, Tumor ; Cell Movement ; Crystallography, X-Ray ; Cytoskeleton - chemistry ; Cytoskeleton - metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Intracellular Signaling Peptides and Proteins - chemistry ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinetics ; Life Sciences ; Membrane Proteins - chemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Microfilament Proteins - chemistry ; Microfilament Proteins - genetics ; Microfilament Proteins - metabolism ; Mutation ; Nerve Tissue Proteins - chemistry ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Nuclear Envelope - metabolism ; Nuclear Matrix - chemistry ; Nuclear Matrix - metabolism ; Nuclear Proteins - chemistry ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Original ; original-article ; Peptides ; Protein Structure, Tertiary ; SUN ; 三聚体 ; 信封 ; 复合物 ; 晶体结构 ; 疏水相互作用 ; 细胞骨架 ; 结构洞</subject><ispartof>Cell research, 2012-10, Vol.22 (10), p.1440-1452</ispartof><rights>Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2012</rights><rights>Copyright Nature Publishing Group Oct 2012</rights><rights>Copyright © 2012 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2012 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-709c961bc3493ea6ed23ee5b865fddb8ba7072e08b50b3d12f2856ab7286dc83</citedby><cites>FETCH-LOGICAL-c472t-709c961bc3493ea6ed23ee5b865fddb8ba7072e08b50b3d12f2856ab7286dc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85240X/85240X.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463262/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463262/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22945352$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Wenjia</creatorcontrib><creatorcontrib>Shi, Zhubing</creatorcontrib><creatorcontrib>Jiao, Shi</creatorcontrib><creatorcontrib>Chen, Cuicui</creatorcontrib><creatorcontrib>Wang, Huizhen</creatorcontrib><creatorcontrib>Liu, Guoguang</creatorcontrib><creatorcontrib>Wang, Qiang</creatorcontrib><creatorcontrib>Zhao, Yun</creatorcontrib><creatorcontrib>Greene, Mark I</creatorcontrib><creatorcontrib>Zhou, Zhaocai</creatorcontrib><title>Structural insights into SUN-KASH complexes across the nuclear envelope</title><title>Cell research</title><addtitle>Cell Res</addtitle><addtitle>Cell Research</addtitle><description>Linker of the nucleoskeleton and the cytoskeleton （LINC） complexes are composed of SUN and KASH domain- containing proteins and bridge the inner and outer membranes of the nuclear envelope. LINC complexes play criti- cal roles in nuclear positioning, cell polarization and cellular stiffness. Previously, we reported the homotrimeric structure of human SUN2. We have now determined the crystal structure of the human SUN2-KASH complex. In the complex structure, the SUN domain homotrimer binds to three independent ＂hook＂-like KASH peptides. The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state. A major conformational change involves the AA＇-loop of KASH-bound SUN domain, which rearranges to form a mini β-sheet that interacts with the KASH peptide. The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain, which we termed the BI-pocket. Moreover, two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding. Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro. In addition, transfection of wild-type, but not mutant, SUN2 promotes cell migration in Ovcar-3 cells. These results provide a structural model of the LINC complex, which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.</description><subject>631/535</subject><subject>Amino Acid Motifs</subject><subject>Binding Sites</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Crystallography, X-Ray</subject><subject>Cytoskeleton - chemistry</subject><subject>Cytoskeleton - metabolism</subject><subject>Humans</subject><subject>Hydrogen Bonding</subject><subject>Hydrophobic and Hydrophilic Interactions</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>Kinetics</subject><subject>Life Sciences</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Microfilament Proteins - chemistry</subject><subject>Microfilament Proteins - genetics</subject><subject>Microfilament Proteins - metabolism</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - chemistry</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Nuclear Envelope - metabolism</subject><subject>Nuclear Matrix - chemistry</subject><subject>Nuclear Matrix - metabolism</subject><subject>Nuclear Proteins - chemistry</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Original</subject><subject>original-article</subject><subject>Peptides</subject><subject>Protein Structure, Tertiary</subject><subject>SUN</subject><subject>三聚体</subject><subject>信封</subject><subject>复合物</subject><subject>晶体结构</subject><subject>疏水相互作用</subject><subject>细胞骨架</subject><subject>结构洞</subject><issn>1001-0602</issn><issn>1748-7838</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkc1PGzEQxS1ExVd74l4t6gUJNh1_rnOphFCBCtQeQs-W1ztJFm3sYO-i9r-vQ0IEFSePND-_eTOPkGMKIwpcf3VxxICyEWVqhxzQSuiy0lzv5hqAlqCA7ZPDlB4AmBSS7pF9xsZCcskOyPWkj4Prh2i7ovWpnc37lIs-FJPfP8vbi8lN4cJi2eEfTIV1MaRU9HMs_OA6tLFA_4RdWOJH8mFqu4SfNu8Rub_6fn95U979uv5xeXFXOlGxvqxg7MaK1o6LMUersGEcUdZayWnT1Lq2FVQMQdcSat5QNmVaKltXTKvGaX5Evq1ll0O9wMah77Nzs4ztwsa_JtjWvO34dm5m4clwoThTLAucbgRieBww9WbRJoddZz2GIRkKmup8Qi4z-uU_9CEM0eftninBQfCV4Nmaer5NxOnWDAWzyse4aFb5mJxPpj-_9r9lXwLJwPkaSLnlZxhfD31P72QzfR787DH_2EoKLjQFAfwfvZ6k2Q</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Wang, Wenjia</creator><creator>Shi, Zhubing</creator><creator>Jiao, Shi</creator><creator>Chen, Cuicui</creator><creator>Wang, Huizhen</creator><creator>Liu, Guoguang</creator><creator>Wang, Qiang</creator><creator>Zhao, Yun</creator><creator>Greene, Mark I</creator><creator>Zhou, Zhaocai</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W94</scope><scope>WU4</scope><scope>~WA</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>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121001</creationdate><title>Structural insights into SUN-KASH complexes across the nuclear envelope</title><author>Wang, Wenjia ; Shi, Zhubing ; Jiao, Shi ; Chen, Cuicui ; Wang, Huizhen ; Liu, Guoguang ; Wang, Qiang ; Zhao, Yun ; Greene, Mark I ; Zhou, Zhaocai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-709c961bc3493ea6ed23ee5b865fddb8ba7072e08b50b3d12f2856ab7286dc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/535</topic><topic>Amino Acid Motifs</topic><topic>Binding Sites</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Crystallography, X-Ray</topic><topic>Cytoskeleton - chemistry</topic><topic>Cytoskeleton - metabolism</topic><topic>Humans</topic><topic>Hydrogen Bonding</topic><topic>Hydrophobic and Hydrophilic Interactions</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>Kinetics</topic><topic>Life Sciences</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Microfilament Proteins - chemistry</topic><topic>Microfilament Proteins - genetics</topic><topic>Microfilament Proteins - metabolism</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - chemistry</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Nuclear Envelope - metabolism</topic><topic>Nuclear Matrix - chemistry</topic><topic>Nuclear Matrix - metabolism</topic><topic>Nuclear Proteins - chemistry</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Original</topic><topic>original-article</topic><topic>Peptides</topic><topic>Protein Structure, Tertiary</topic><topic>SUN</topic><topic>三聚体</topic><topic>信封</topic><topic>复合物</topic><topic>晶体结构</topic><topic>疏水相互作用</topic><topic>细胞骨架</topic><topic>结构洞</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Wenjia</creatorcontrib><creatorcontrib>Shi, Zhubing</creatorcontrib><creatorcontrib>Jiao, Shi</creatorcontrib><creatorcontrib>Chen, Cuicui</creatorcontrib><creatorcontrib>Wang, Huizhen</creatorcontrib><creatorcontrib>Liu, Guoguang</creatorcontrib><creatorcontrib>Wang, Qiang</creatorcontrib><creatorcontrib>Zhao, Yun</creatorcontrib><creatorcontrib>Greene, Mark I</creatorcontrib><creatorcontrib>Zhou, Zhaocai</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-自然科学</collection><collection>中文科技期刊数据库-自然科学-生物科学</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Wenjia</au><au>Shi, Zhubing</au><au>Jiao, Shi</au><au>Chen, Cuicui</au><au>Wang, Huizhen</au><au>Liu, Guoguang</au><au>Wang, Qiang</au><au>Zhao, Yun</au><au>Greene, Mark I</au><au>Zhou, Zhaocai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural insights into SUN-KASH complexes across the nuclear envelope</atitle><jtitle>Cell research</jtitle><stitle>Cell Res</stitle><addtitle>Cell Research</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>22</volume><issue>10</issue><spage>1440</spage><epage>1452</epage><pages>1440-1452</pages><issn>1001-0602</issn><eissn>1748-7838</eissn><abstract>Linker of the nucleoskeleton and the cytoskeleton （LINC） complexes are composed of SUN and KASH domain- containing proteins and bridge the inner and outer membranes of the nuclear envelope. LINC complexes play criti- cal roles in nuclear positioning, cell polarization and cellular stiffness. Previously, we reported the homotrimeric structure of human SUN2. We have now determined the crystal structure of the human SUN2-KASH complex. In the complex structure, the SUN domain homotrimer binds to three independent ＂hook＂-like KASH peptides. The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state. A major conformational change involves the AA＇-loop of KASH-bound SUN domain, which rearranges to form a mini β-sheet that interacts with the KASH peptide. The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain, which we termed the BI-pocket. Moreover, two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding. Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro. In addition, transfection of wild-type, but not mutant, SUN2 promotes cell migration in Ovcar-3 cells. These results provide a structural model of the LINC complex, which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>22945352</pmid><doi>10.1038/cr.2012.126</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/535 Amino Acid Motifs Binding Sites Biomedical and Life Sciences Cell Biology Cell Line, Tumor Cell Movement Crystallography, X-Ray Cytoskeleton - chemistry Cytoskeleton - metabolism Humans Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Intracellular Signaling Peptides and Proteins - chemistry Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Kinetics Life Sciences Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Microfilament Proteins - chemistry Microfilament Proteins - genetics Microfilament Proteins - metabolism Mutation Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Nuclear Envelope - metabolism Nuclear Matrix - chemistry Nuclear Matrix - metabolism Nuclear Proteins - chemistry Nuclear Proteins - genetics Nuclear Proteins - metabolism Original original-article Peptides Protein Structure, Tertiary SUN 三聚体 信封 复合物 晶体结构 疏水相互作用 细胞骨架 结构洞 |
| title | Structural insights into SUN-KASH complexes across the nuclear envelope |
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