Biophysics and Biochemistry of Macromolecular Interactions
Group leader
Cesar Martin & Helena Ostolaza
Phone
+34 94 601 8052 / +34 94 601 5538
Address
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
Cesar Augusto Martin
University Lecturer
Helena Ostolaza
University Professor
Publications
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
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.
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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