Architecture of the cytoplasmic face of the nuclear pore

被引：74

作者：

Bley, Christopher J. ^{[1
]}

Nie, Si ^{[1
]}

Mobbs, George W. ^{[1
]}

Petrovic, Stefan ^{[1
]}

Gres, Anna T. ^{[1
,6
]}

Liu, Xiaoyu ^{[1
,7
]}

Mukherjee, Somnath ^{[2
]}

Harvey, Sho ^{[1
]}

Huber, Ferdinand M. ^{[1
,8
]}

Lin, Daniel H. ^{[1
,9
]}

Brown, Bonnie ^{[1
]}

Tang, Aaron W. ^{[1
]}

Rundlet, Emily J. ^{[1
,10
,11
]}

Correia, Ana R. ^{[1
,12
]}

Chen, Shane ^{[3
]}

Regmi, Saroj G. ^{[3
]}

Stevens, Taylor A. ^{[1
]}

Jette, Claudia A. ^{[1
]}

Dasso, Mary ^{[3
]}

Patke, Alina ^{[4
]}

Palazzo, Alexander F. ^{[5
]}

Kossiakoff, Anthony A. ^{[2
]}

Hoelz, Andre ^{[1
]}

机构：

[1] CALTECH, Div Chem & Chem Engn, 1200 East Calif Blvd, Pasadena, CA 91125 USA

[2] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA

[3] NICHHD, Div Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA

[4] CALTECH, Div Biol & Biol Engn, 1200 East Calif Blvd, Pasadena, CA 91125 USA

[5] Univ Toronto, Dept Biochem, Toronto, ON M5G 1M1, Canada

[6] Worldwide Clin Trials, Sci Solut, Clin Res Methodol, 600 Pk Off Dr Suite 200, Res Triangle Pk, NC 27709 USA

[7] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, 609 Charles E Young Dr East, Los Angeles, CA 90095 USA

[8] Odyssey Therapeut Inc, Ind Pk Hochst G875, D-65926 Frankfurt, Germany

[9] Whitehead Inst Biomed Res, 455 Main St, Cambridge, MA 02142 USA

[10] St Jude Childrens Res Hosp, Dept Struct Biol, 262 Danny Thomas Pl, Memphis, TN 38105 USA

[11] Weill Cornell Med, Triinst PhD Program Chem Biol, 1300 York Ave, New York, NY 10065 USA

[12] Amgen Inc, Amgen Res, One Amgen Ctr Dr, Thousand Oaks, CA 91320 USA

来源：

SCIENCE | 2022年 / 376卷 / 6598期

基金：

美国国家卫生研究院;

关键词：

MESSENGER-RNA EXPORT; N-TERMINAL DOMAIN; ACUTE NECROTIZING ENCEPHALOPATHY; BOX PROTEIN DBP5; CRYSTAL-STRUCTURE; FUNCTIONAL-ANALYSIS; INNER RING; MOLECULAR ARCHITECTURE; NUCLEOPORIN COMPLEX; CONSERVED MECHANISM;

D O I：

10.1126/science.abm9129

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating the NPC symmetric core architecture, the asymmetrically decorated cytoplasmic face, essential for messenger RNA (mRNA) export and a hotspot for nucleoporin-associated diseases, has remained elusive. Here we report a composite structure of the human cytoplasmic face obtained by combining biochemical reconstitution, crystal structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation. Whereas species-specific motifs anchor an evolutionarily conserved similar to 540-kilodalton heterohexameric cytoplasmic filament nucleoporin complex above the central transport channel, attachment of the NUP358 pentameric bundles depends on the double-ring arrangement of the coat nucleoporin complex. Our composite structure and its predictive power provide a rich foundation for elucidating the molecular basis of mRNA export and nucleoporin diseases.

引用

页码：1174 / +

页数：293

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