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The Structure of the Nuclear Pore Complex (An Update)

Lin, Daniel H. and Hoelz, André (2019) The Structure of the Nuclear Pore Complex (An Update). Annual Review of Biochemistry, 88 . pp. 725-783. ISSN 0066-4154. PMCID PMC6588426.

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The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (∼1,000 protein subunits, ∼110 MDa in humans), the NPC has remained one of the foremost challenges for structure determination. Structural studies have now provided atomic-resolution crystal structures of most nucleoporins. The acquisition of these structures, combined with biochemical reconstitution experiments, cross-linking mass spectrometry, and cryo–electron tomography, has facilitated the determination of the near-atomic overall architecture of the symmetric core of the human, fungal, and algal NPCs. Here, we discuss the insights gained from these new advances and outstanding issues regarding NPC structure and function. The powerful combination of bottom-up and top-down approaches toward determining the structure of the NPC offers a paradigm for uncovering the architectures of other complex biological machines to near-atomic resolution.

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Hoelz, André0000-0003-1726-0127
Additional Information:© 2019 Annual Reviews. Review in Advance first posted on March 18, 2019. The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review. We apologize to our colleagues whose work was not discussed adequately owing to space constraints. We thank all current and former members of the Hoelz laboratory for their dedication, insight, and camaraderie, which have made our laboratory's contributions to the advances in NPC structure possible; Ferdinand Huber, George Mobbs, Si Nie, Alina Patke, and Stefan Petrovic for critical reading of the manuscript; and Valerie Altounian for the preparation of the animations and NPC schematics. We acknowledge Martin Beck for sharing the C. reinhardtii NPC cryo-ET reconstruction prior to publication for production of figures. A.H. is an Investigator of the Heritage Medical Research Institute and a Faculty Scholar of the Howard Hughes Medical Institute and was supported by National Institutes of Health grants R01-GM111461 and R01-GM117360 and a Camille Dreyfus Teacher-Scholar Award from the Camille and Henry Dreyfus Foundation.
Group:Heritage Medical Research Institute
Funding AgencyGrant Number
Heritage Medical Research InstituteUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Camille and Henry Dreyfus FoundationUNSPECIFIED
Subject Keywords:nuclear pore complex, nucleocytoplasmic transport, mRNA export, integrative structural biology, X-ray crystallography, electron microscopy
PubMed Central ID:PMC6588426
Record Number:CaltechAUTHORS:20190325-111006962
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Official Citation:The Structure of the Nuclear Pore Complex (An Update). Daniel H. Lin and André Hoelz. Annual Review of Biochemistry 2019 88:1, 725-783; doi: 10.1146/annurev-biochem-062917-011901
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94119
Deposited By: Tony Diaz
Deposited On:25 Mar 2019 18:24
Last Modified:15 Jan 2020 00:23

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