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Structural insights into SUN-KASH complexes across the nuclear envelope | |
2012 | |
发表期刊 | CELL RESEARCH
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ISSN | 1001-0602 |
EISSN | 1748-7838 |
卷号 | 22期号:10页码:144-1452 |
发表状态 | 已发表 |
DOI | 10.1038/cr.2012.126 |
摘要 | 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 critical 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 beta-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. |
关键词 | crystal structure SUN2 KASH LINC complexes mechanical force transduction nuclear envelope |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000309518300009 |
出版者 | NATURE PUBLISHING GROUP |
WOS关键词 | LINC COMPLEXES ; PROTEINS ; LOCALIZATION ; MIGRATION ; MATEFIN/SUN-1 ; LAMINOPATHIES ; REQUIREMENTS ; TELOMERES ; NESPRIN-2 ; FEATURES |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119883 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Zhou, Zhaocai |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 2.Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA 3.Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA |
推荐引用方式 GB/T 7714 | Wang, Wenjia,Shi, Zhubing,Jiao, Shi,et al. Structural insights into SUN-KASH complexes across the nuclear envelope[J]. CELL RESEARCH,2012,22(10):144-1452. |
APA | Wang, Wenjia.,Shi, Zhubing.,Jiao, Shi.,Chen, Cuicui.,Wang, Huizhen.,...&Zhou, Zhaocai.(2012).Structural insights into SUN-KASH complexes across the nuclear envelope.CELL RESEARCH,22(10),144-1452. |
MLA | Wang, Wenjia,et al."Structural insights into SUN-KASH complexes across the nuclear envelope".CELL RESEARCH 22.10(2012):144-1452. |
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