Integrative Structural and Functional Characterization of Macromolecular Assemblies

Group leader
Javier Fernández Martínez

Biofisika Institute (CSIC-UPV/EHU)
Science Park of the UPV/EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)

Research goal

Our laboratory is interested in the structural and functional characterization of macromolecular assemblies, with special emphasis on the large protein complex that regulates transport between the nucleus and the cytoplasm in eukaryotic cells: the nuclear pore complex (NPC). Apart from its main role as mediator of nucleocytoplasmic transport, the NPC is also a key platform for the regulation of many essential nuclear processes, such as chromatin organization, gene expression, or DNA repair. It is thus not surprising that defects affecting the NPC function are directly related to severe human diseases, like several types of cancers and neurological disorders. To understand how the NPC performs its roles we use a combination of approaches, including biochemical, proteomic, cell and structural biology methods, that are finally combined into integrative structure-function maps to reveal the basic molecular mechanisms underlying the NPC function.

Group members

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Akey CW, Echeverria I, Ouch C, Nudelman I, Shi Y, Wang J, Chait BT, Sali A, Fernandez-Martinez J, Rout MP
Implications of a multiscale structure of the yeast nuclear pore complex
Mol Cell. 2023 Sep 21;83(18):3283-3302.e5
doi: 10.1016/j.molcel.2023.08.025

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Markert J, Luger K, Lee H, Hu H, Taylor NMI, Fernandez-Martinez J, Rout M, Alder N
Depicting protein structures as schematics
Trends Biochem Sci. 2023 Apr;48(4):307-310
doi: 10.1016/j.tibs.2023.01.006

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Nudelman I, Fernandez-Martinez J, Rout MP
Affinity Isolation of Endogenous Saccharomyces Cerevisiae Nuclear Pore Complexes
Methods Mol Biol. 2022;2502:3-34
doi: 10.1007/978-1-0716-2337-4_1

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Akey CW, Singh D, Ouch C, Echeverria I, Nudelman I, Varberg JM, Yu Z, Fang F, Shi Y, Wang J, Salzberg D, Song K, Xu C, Gumbart JC, Suslov S, Unruh J, Jaspersen SL, Chait BT, Sali A, Fernandez-Martinez J, Ludtke SJ, Villa E, Rout MP.

Comprehensive structure and functional adaptations of the yeast nuclear pore complex
Cell. 2022 Jan 20;185(2):361-378.e25
DOI: 10.1016/j.cell.2021.12.015

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Ricardo-Lax I, Luna JM, Thao TTN, Le Pen J, Yu Y, Hoffmann HH, Schneider WM, Razooky BS, Fernandez-Martinez J, Schmidt F, Weisblum Y, Trüeb BS, Berenguer Veiga I, Schmied K, Ebert N, Michailidis E, Peace A, Sánchez-Rivera FJ, Lowe SW, Rout MP, Hatziioannou T, Bieniasz PD, Poirier JT, MacDonald MR, Thiel V, Rice CM.

Replication and single-cycle delivery of SARS-CoV-2 replicons
Science. 2021 Nov 26;374(6571):1099-1106
DOI: 10.1126/science.abj8430

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Hakhverdyan Z, Molloy KR, Subbotin RI, Fernandez-Martinez J, Chait BT, Rout MP

Measuring in vivo protein turnover and exchange in yeast macromolecular assemblies
STAR Protoc. 2021 Sep 8;2(3):100800
DOI: 10.1016/j.xpro.2021.100800

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Fernandez-Martinez J, Rout MP.

One Ring to Rule them All? Structural and Functional Diversity in the Nuclear Pore Complex. Trends in Biochemical Sciences. 2021 Jul;46(7):595-607. PMID: 33563541. First author.
Trends Biochem Sci. 2021 Jul;46(7):595-607
DOI: 10.1016/j.tibs.2021.01.003

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Hakhverdyan Z, Molloy KR, Keegan S, Herricks T, Lepore DM, Munson M, Subbotin RI, Fenyo D, Aitchison JD, Fernandez-Martinez J, Chait BT, Rout MP

Dissecting the structural dynamics of the nuclear pore complex.
Mol Cell. 2021 Jan 7;81(1):153-165.e7
DOI: 10.1016/j.molcel.2020.11.032

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Kim SJ, Fernandez-Martinez J, Nudelman I, Shi Y, Zhang W, Raveh B, Herricks T, Slaughter BD, Hogan J, Upla P, Chemmama IE, Pellarin R, Echeverria I, Shivaraju M, Chaudhury AS, Wang J, Williams R, Unruh JR, Greenberg CH, Jacobs EY, Yu Z, de la Cruz MJ, Mironska R, Stokes DL, Aitchison JD, Jarrold MF, Gerton JL, Ludtke SJ, Akey CW, Chait BT, Sali A, Rout MP.

Integrative Structure and Functional Anatomy of a Nuclear Pore Complex.
Nature. 2018 Mar 22;555(7697):475-482
DOI: 10.1038/nature26003