Structural Biology of Disease Mechanisms

Group leader
Iban Ubarretxena
Address

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

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Research goal

We employ high-resolution cryo-electron microscopy (cryo-EM), in combination with functional experiments, to uncover the structure and mechanism of action of macromolecular protein complexes involved in human disease. The goal of our research is to open new therapeutic avenues by understanding the role of these protein complexes in pathogenesis.

Group members
Postdoctoral Fellow
Distinguished University Researcher / Ikerbasque Research Professor / Director of IBF and FBB / Scientific Director BREM
Postdoctoral Fellow
Protein Biochemistry Specialist
JAE Intro Intern
Publications

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Jabalera Y, Tascón I, Samperio S, López-Alonso JP, Gonzalez-Lopez M, Aransay AM, Abascal-Palacios G, Beisel CL, Ubarretxena-Belandia I, Perez-Jimenez R

A resurrected ancestor of Cas12a expands target access and substrate recognition for nucleic acid editing and detection
Nat Biotechnol. 2024 Oct 31
doi: 10.1038/s41587-024-02461-3

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Bernal-Bernal D, Pantoja-Uceda D, López-Alonso JP, López-Rojo A, López-Ruiz JA, Galbis-Martínez M, Ochoa-Lizarralde B, Tascón I, Elías-Arnanz M, Ubarretxena-Belandia I, Padmanabhan S

Structural basis for regulation of a CBASS-CRISPR-Cas defense island by a transmembrane anti-σ factor and its ECF σ partner
Sci Adv. 2024 Oct 25;10(43):eadp1053
doi: 10.1126/sciadv.adp1053

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Malik R, Johnson RE, Ubarretxena-Belandia I, Prakash L, Prakash S, Aggarwal AK
Cryo-EM structure of the Rev1-Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis
Nat Struct Mol Biol. 2024 May 8
doi: 10.1038/s41594-024-01302-w

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González-Magaña A, Tascón I, Altuna-Alvarez J, Queralt-Martín M, Colautti J, Velázquez C, Zabala M, Rojas-Palomino J, Cárdenas M, Alcaraz A, Whitney JC, Ubarretxena-Belandia I, Albesa-Jové D
Structural and functional insights into the delivery of a bacterial Rhs pore-forming toxin to the membrane
Nat Commun. 2023 Nov 28;14(1):7808
doi: 10.1038/s41467-023-43585-5

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Fuss MF, Wieferig JP, Corey RA, Hellmich Y, Tascón I, Sousa JS, Stansfeld PJ, Vonck J, Hänelt I
Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation
Nat Commun. 2023 Jun 21;14(1):3683
doi: 10.1038/s41467-023-38944-1

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Malik R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I and Aggarwal AK

Cryo-EM structure of translesion DNA synthesis polymerase ζ with a base pair mismatch
Nat Commun. 2022 Feb 25;13(1):1050.
DOI: 10.1038/s41467-022-28644-7

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de la Arada I, Torralba J, Tascón I, Colom A, Ubarretxena-Belandia I, Arrondo JLR, Apellániz B, Nieva JL.

Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope.
Sci Rep. 2021 Jan 14;11(1):1278.
DOI: 10.1038/s41598-020-80156-w

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Tascón I, Sousa JS, Corey RA, Mills DJ, Griwatz D, Aumüller N, Mikusevic V, Stansfeld PJ, Vonck J, Hänelt I.

Structural basis of proton-coupled potassium transport in the KUP family.
Nat Commun. 2020 Jan 31;11(1):626
DOI: 10.1038/s41467-020-14441-7

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Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK

Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.
Nat Struct Mol Biol. 2020 Oct;27(10):913-924.
DOI: 10.1038/s41594-020-0476-7

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Gomez-Llorente Y, Jebara F, Patra M, Malik R, Shahar Nisemblat S, Chomsky-Hecht O,Parnas A, Azem A, Hirsch JA, Ubarretxena-Belandia I.

Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin.
Nat Commun. 2020 Jun 20;10(1):2699.
DOI: 10.1038/s41467-020-15698-8

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Jain R, Rice WJ, Malik R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK.

Cryo-EM structure and dynamics of eukaryotic DNA polymerase δ holoenzyme.
Nat Struct Mol Biol. 2019 Oct;26(10):955-962.
DOI: 10.1038/s41594-019-0305-z

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Stein KR, Gardner TJ, Hernandez RE, Kraus TA, Duty JA, Ubarretxena-Belandia I, Moran TM, Tortorella D.

CD46 facilitates entry and dissemination of human cytomegalovirus.
Nat Commun. 2019 Jun 20;10(1):2699.
DOI: 10.1038/s41467-019-10587-1

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Schaffner A, Li X, Gomez-Llorente Y, Leandrou E, Memou A, Clemente N, Yao C, Afsari F, Zhi L, Pan N, Morohashi K, Hua X, Zhou MM, Wang C, Zhang H, Chen SG, Elliott CJ, Rideout H, Ubarretxena-Belandia I, Yue Z.

Vitamin B(12) modulates Parkinson's disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection.
Cell Res. 2019 Apr;29(4):313-329.
DOI: 10.1038/s41422-019-0153-8

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Stock C, Hielkema L, Tascón I, Wunnicke D, Oostergetel GT, Azkargorta M,Paulino C, Hänelt I.

Cryo-EM structures of KdpFABC suggest a K(+) transportmechanism via two inter-subunit half-channels.
Nat Commun. 2018 Nov 26;9(1):4971.
DOI: 10.1038/s41467-018-07319-2

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Brown MC, Abdine A, Chavez J, Schaffner A, Torres-Arancivia C, Lada B, JiJi RD, Osman R, Cooley JW, Ubarretxena-Belandia I.

Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.
Biophys J. 2018 Apr 10;114(7):1579-1589.
DOI: 10.1016/j.bpj.2018.01.043

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Ken Y. Hui, Heriberto Fernandez-Hernandez, Jianzhong Hu, Adam Schaffner, Nathan Pankratz, Shai Carmi, Nicole Villaverde, Xianting Li, Manual Rivas, Adam P. Levine, Xiuliang Bao, Philippe R. Labrias, Talin Haritunians, Darren Ruane, Beatrice Monica Bowen, Elena R. Schiff, Nikolas Pontikos, Nir Barzilai, Steven R. Brant, Susan Bressman, Adam S. Cheifetz, Lorraine N. Clark, Mark J. Daly, Robert Desnick, Richard H. Duerr, Seymour Katz, Todd Lencz, Dermot P.B. McGovern, Richard H. Myers, Harry Ostrer, Laurie Ozelius, Haydeh Payami, Yakov Peter, John D. Rioux, Anthony Segal, William K. Scott, Mark S. Silverberg, Jeffery M. Vance, Tatiana Foroud, Gil Atzmon, Itsik Pe’er, Yiannis Ioannou, Iban Ubarretxena-Belandia, Zhenyu Yue, Eric E. Schadt, Judy H. Cho, Inga Peter.

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease.
Sci Transl Med. 2018 Jan 10;10(423).
DOI: 10.1126/scitranslmed.aai7795