Integrative Structural and Functional Characterization of Macromolecular Assemblies Laboratory

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

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. PMID: 34982960. *Co-corresponding author.
doi: 10.1016/j.cell.2021.12.015

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. PMID: 34648371.
doi: 10.1126/science.abj8430

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 Protocols. 2021 Sep 8;2(3):100800. PMID: 34527957. *Co-corresponding author.
doi: 10.1016/j.xpro.2021.100800

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.
doi: 10.1016/j.tibs.2021.01.003

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. Molecular Cell. 2021 Jan 7;81(1):153-165.e7. PMID: 33333016. *Co-corresponding author.
doi: 10.1016/j.molcel.2020.11.032

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, Sali1 A, Rout MP.

Integrative Structure and Functional Anatomy of a Nuclear Pore Complex. Nature. 2018 Mar 22;555(7697):475-482. PMID: 29539637. *Co-first author.
doi: 10.1038/nature26003