Biophysics and Biochemistry of Macromolecular Interactions

Group leader
Cesar Martin & Helena Ostolaza
Phone
+34 94 601 8052 / +34 94 601 5538
Address

cesar.martin@ehu.eus

elenaamaya.ostolaza@ehu.eus

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

Research goal

We are an interdisciplinary research group combining biophysical, cell biology, biochemistry and molecular biology methodologies. Two are our main research focuses are:

  • The study of the molecular mechanisms that underlie protein-protein and protein-membrane interactions, using bacterial toxins as a model system, in particular, the adenylate cyclase toxins, which are essential virulence factors produced by different bacterial pathogens (e.g. Bordetella pertussis, Escherichia coli).
  • Understanding the molecular mechanism that leads to genetic/hereditary hypercholesterolemia and cardiovascular disease. We do translational research by assessing pathogenic variants of LDLR, ApoB-100 and PCSK9 to provide a certain genetic diagnosis of the disease.
Group members
University Lecturer
University Professor
Publications

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Mercado-Gómez M, Goikoetxea-Usandizaga N, Giné AE, Merlos Rodrigo MA, Afonso MB, Azkargorta M, Zapata-Pavas LE, Rejano-Gordillo CM, Romero MR, Mendizabal I, Rodrigues PM, Wu H, Rodríguez-Agudo R, Serrano-Maciá M, Olaizola P, Barrenechea-Barrenechea JA, González Recio I, G Fernandez-Barrena M, Overi D, Gaudio E, Schaeper U, Garcia-Longarte S, Yáñez-Bartolomé M, Peña-SanFelix P, Gil-Pitarch C, Lapitz A, Michalkova H, Heger Z, Conter C, Macias RIR, Carracedo A, Bañales J, Moreno V, Lamarca A, Singh R, Delgado TC, Martínez-Cruz LA, Elortza F, Avila MA, Martín C, Tian TV, Macarulla T, Buccella D, Cubero FJ, Calvisi DF, Carpino G, Marin JJG, Rodrigues CMP, Martinez-Chantar ML

Role of CNNM4 in the progression of cholangiocarcinoma: implications for ferroptosis and therapeutic potential
Gut. 2026 Jan 8;75(2):341-352. PMID: 40764063.
doi: 10.1136/gutjnl-2024-333255

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González-Recio I, Goikoetxea-Usandizaga N, Rejano-Gordillo CM, Conter C, Rodríguez Agudo R, Serrano-Maciá M, Zapata-Pavas LE, Peña-Sanfélix P, Azkargorta M, Elortza F, Herranz JM, Guillamon Thiery Á, Guerra-Ruiz AR, Jover R, Galicia-Garcia U, Martín C, Schaeper U, Delgado TC, Díaz-Moreno I, Díaz Quintana A, Buccella D, Nogueiras R, Argemi J, Ávila MA, Gratacós-Ginès J, Iruzubieta P, Pose E, Bataller R, Crespo J, Martínez-Cruz LA, Martínez-Chantar ML

Modulatory effects of CNNM4 on Protein-L-Isoaspartyl-O-Methyltransferase repair function during Alcohol-Induced hepatic damage
Hepatology. 2025 Aug 1;82(2):388-404. Epub 2024 Nov 19. PMID: 39641635; PMCID: PMC12266796.
10.1097/HEP.0000000000001156

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Arrasate A, Lopez-Robles C, Zuazo M, Banos-Mateos S, Martin C, Lamsfus-Calle A, Fertin MJ.

Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors
Int J Mol Sci. 2025 Sep 1;26(17):8497. PMID: 40943418; PMCID: PMC12429303.
10.3390/ijms26178497.

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Gomez-Larrauri A, Benito-Vicente A, Larrea-Sebal A, Martín C, Gomez-Muñoz A

Role of Ceramide Kinase/C1P in the Regulation of Cell Growth and Survival
Int J Mol Sci. 2025 Aug 28;26(17):8374. PMID: 40943293; PMCID: PMC12429069.
10.3390/ijms26178374.

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Gomez-Larrauri A, Larrea-Sebal A, Martín C, Gomez-Muñoz A. 

The critical roles of bioactive sphingolipids in inflammation
J Biol Chem. 2025 Aug;301(8):110475. Epub 2025 Jul 11. PMID: 40653199; PMCID: PMC12340401.
10.1016/j.jbc.2025.110475

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Ostolaza H, Amuategi J

Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity
Int J Mol Sci. 2024 Mar 8;25(6):3131
doi: 10.3390/ijms25063131

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Alloza-Moral I, Aldekoa-Etxabe A, Tulloch-Navarro R, Fiat-Arriola A, Mar C, Urrechaga E, Ponga C, Artiga-Folch I, Garcia-Bediaga N, Aspichueta P, Martin C, Zarandona-Garai A, Pérez-Fernández S, Arana-Arri E, Triviño JC, Uranga A, España PP, Vandenbroeck-van-Caeckenbergh K

Genetic Analysis and Predictive Modeling of COVID-19 Severity in a Hospital-Based Patient Cohort
Biomolecules. 2025 Mar 10;15(3):393. PMID: 40149929; PMCID: PMC11940120.
10.3390/biom15030393

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Larrea-Sebal A, Sasiain I, Jebari-Benslaiman S, Galicia-Garcia U, Uribe KB, Benito-Vicente A, Gracia-Rubio I, Bediaga-Bañeres H, Arrasate S, Cenarro A, Civeira F, González-Díaz H, Martín C

OptiMo-LDLr: An Integrated In Silico Model with Enhanced Predictive Power for LDL Receptor Variants, Unraveling Hot Spot Pathogenic Residues
Adv Sci (Weinh). 2024 Jan 23:e2305177
doi: 10.1002/advs.202305177

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Jebari-Benslaiman S, Larrea-Sebal A, Benito-Vicente A, Martín C.

Cardiovascular Disease, Atherosclerosis and Familial Hypercholesterolemia: From Molecular Mechanisms Causing Pathogenicity to New Therapeutic Approaches
Int J Mol Sci. 2023 Apr 21;24(8):7659
doi: 10.3390/ijms24087659

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Amuategi J, Alonso R, Ostolaza H

Four Cholesterol-Recognition Motifs in the Pore-Forming and Translocation Domains of Adenylate Cyclase Toxin Are Essential for Invasion of Eukaryotic Cells and Lysis of Erythrocytes
Int J Mol Sci. 2022 Aug 5;23(15):8703
doi: 10.3390/ijms23158703

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Jebari-Benslaiman S, Uribe KB, Benito-Vicente A, Galicia-Garcia U, Larrea-Sebal A, Santin I, Alloza I, Vandenbroeck K, Ostolaza H, Martín C

Boosting Cholesterol Efflux from Foam Cells by Sequential Administration of rHDL to Deliver MicroRNA and to Remove Cholesterol in a Triple-Cell 2D Atherosclerosis Model
Small. 2022 Apr;18(13):e2105915
doi: 10.1002/smll.202105915

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Larrea-Sebal A, Benito-Vicente A, Fernandez-Higuero JA, Jebari-Benslaiman S, Galicia-Garcia U, Uribe KB, Cenarro A, Ostolaza H, Civeira F, Arrasate S, González-Díaz H, Martín C

MLb-LDLr: A Machine Learning Model for Predicting the Pathogenicity of LDLr Missense Variants
JACC Basic Transl Sci. 2021 Nov 22;6(11):815-827
doi: 10.1016/j.jacbts.2021.08.009

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Galicia-Garcia, U., Benito-Vicente, A., Uribe, K.B., Jebari, S., Larrea-Sebal, A., Alonso-Estrada, R., Aguilo-Arce, J., Ostolaza, H., Palacios, L., Martin, C.

Mutation type classification and pathogenicity assignment of sixteen missense variants located in the EGF-precursor homology domain of the LDLR
Sci Rep. 2020 Feb 3;10(1):1727.
DOI: 10.1038/s41598-020-58734-9

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Sánchez-Hernández, R.M., Di Taranto, M.D., Benito-Vicente, A., Uribe, K.B., Lamiquiz-Moneo, I., Larrea-Sebal, A., Jebari, S., Galicia-Garcia, U., Nóvoa, F.J., Boronat, M., Wägner, A.M., Civeira, F., Martín, C., Fortunato, G.

The Arg499His gain-of-function mutation in the C-terminal domain of PCSK9
Atherosclerosis. 2019 Oct:289:162-172.
DOI: 10.1016/j.atherosclerosis.2019.08.020

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Ostolaza, H., González-Bullón, D., Uribe, K.B., Martín, C., Amuategi, J., Fernandez-Martínez, X.

Membrane permeabilization by pore-forming rtx toxins: What kind of lesions do these toxins form?
Toxins (Basel). 2019 Jun; 11(6): 354.
DOI: 10.3390/toxins11060354

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González-Bullón, D., Uribe, K.B., Largo, E., Guembelzu, G., García-Arribas, A.B., Martín, C., Ostolaza, H.

Membrane permeabilization by bordetella adenylate cyclase toxin involves pores of tunable size
Biomolecules. 2019 May 10;9(5):183.
DOI: 10.3390/biom9050183

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Etxaniz, A., González-Bullón, D., Martín, C., Alonso, M.T., Ostolaza, H.

Irreversible versus repairable membrane poration: differences in permeabilization elicited by Bordetella Adenylate Cyclase Toxin and its hemolysin domain in macrophages
FEBS J. 2020 May;287(9):1798-1815.
DOI: 10.1111/febs.15106

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Banerjee, P., Chan, K. C., Tarabocchia, M., Benito-Vicente, A., Alves, A.C., Uribe, K.B., Bourbon, M., Skiba, P.J., Pordy, R., Gipe, D.A., Gaudet, D., Martin, C.

Functional analysis of LDLR (low-density lipoprotein receptor) variants in patient lymphocytes to assess the effect of evinacumab in homozygous familial hypercholesterolemia patients with a spectrum of LDLR activity
Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2248-2260.
DOI: 10.1161/ATVBAHA.119.313051

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González-Bullón, D., Martín, C., Ostolaza, H.

Characterization of the intrinsic phospholipase A1 activity of bordetella pertussis adenylate cyclase toxin
Toxins (Basel). 2018 Dec 4;10(12):514.
DOI: 10.3390/toxins10120514

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Benito-Vicente, A., Siddiqi, H., Uribe, K.B., Jebari, S., Galicia-Garcia, U., Larrea-Sebal, A., Stef, M., Ostolaza, H., Palacios, L., Martin, C.

p.(Asp47Asn) and p.(Thr62Met): non deleterious LDL receptor missense variants functionally characterized in vitro
Sci Rep. 2018 Nov 9;8(1):16614.
DOI: 10.1038/s41598-018-34715-x

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Benito-Vicente, A., Uribe, K.B., Jebari, S., Galicia-Garcia, U., Ostolaza, H., Martin, C.

Validation of LDLr activity as a tool to improve genetic diagnosis of familial hypercholesterolemia: A retrospective on functional characterization of LDLr variants
Int J Mol Sci. 2018 Jun 5;19(6):1676.
DOI: 10.3390/ijms19061676

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González-Bullón D, Uribe KB, Martín C, Ostolaza H.

Phospholipase A activity of adenylate cyclase toxin mediates translocation of its adenylate cyclase domain.
Proc Natl Acad Sci USA. 2017 Aug 15;114(33):E6784-E6793.
DOI: 10.1073/pnas.1701783114