creating a
healthier future

Biomolecular Structure & Function

ABOUT

The Biomolecular Structure and Function (BMSF) group focuses on the structural and functional characterisation of biomedically relevant proteins, with a special emphasis on understanding the modulatory role of post-translational modifications and intermolecular interactions on protein function. X-ray crystallography constitutes the core methodology, complemented with other biophysical and biochemical techniques.

 

RESEARCH

The current research lines comprise the structural and functional characterization of the molecular mechanisms of action and regulation of mammalian proteolytic enzymes associated with human neurodegenerative diseases and blood coagulation and of novel drug targets from bacterial and fungal human pathogens.

Briefly, the research group is involved in:

1) Elucidating the molecular mechanisms of self-assembly of a polyglutamine repeat protein, ataxin-3, and developing strategies to modulate this process;
2) Characterising the structure and inhibition mechanism of natural anticoagulants and its regulation by post-translational modifications;
3) Studying the unique structural features of proteins from mycobacterial and fungal human pathogens.

Detail of the experimental electron density map of an essential mycobacterial sugar-processing enzyme at atomic resolution.

Team

Selected Publications

Sárkány Z., Damásio J., Macedo-Ribeiro S., Martins P.M.
Association between the use of levodopa/carbidopa, Alzheimer's disease biomarkers, and cognitive decline among participants in the National Alzheimer's Coordinating Center Uniform Data Set. Alzheimer's and Dementia21(5):, 2025. [Journal: Article] [CI: 2] [IF: 11.1 (*)]
DOI: 10.1002/alz.70213 SCOPUS: 105005264561

Sárkány Z., Figueiredo F., Macedo-Ribeiro S., Martins P.M.
NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation. Molecular Biology of the Cell35(3):, 2024. [Journal: Article] [CI: 2] [IF: 2.7]
DOI: 10.1091/mbc.E23-07-0289 SCOPUS: 85184344567

Felício D., Martins S., Alves G.P., Amorim A., Macedo-Ribeiro S., Merski M.
Evolutionary model of repeat insertions in Ataxin-3 traces the origin of the polyglutamine stretch to an ancestral ubiquitin binding module. Protein Science33(12):, 2024. [Journal: Article] [IF: 5.2]
DOI: 10.1002/pro.5236 SCOPUS: 85210560651

Buxbaum J.N., Eisenberg D.S., Fändrich M., McPhail E.D., Merlini G., Saraiva M.J.M., Sekijima Y., Westermark P.
Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid31(4):249-256, 2024. [Journal: Article] [CI: 39] [IF: 7.4]
DOI: 10.1080/13506129.2024.2405948 SCOPUS: 85205583967

Teixeira C., Martins H.S., Saraiva M.J.
Cellular environment of TTR deposits in an animal model of ATTR—Cardiomyopathy. Frontiers in Molecular Biosciences10:, 2023. [Journal: Article] [CI: 5] [IF: 5,0 (*)]
DOI: 10.3389/fmolb.2023.1144049 SCOPUS: 85150717436

Moreira J., Martins H., Saraiva M., João Saraiva M.
TLR2 and 4 signaling pathways are altered in macrophages from V30M TTR mice with down-regulated expression of chemokines. Clinical Science137(5):355-366, 2023. [Journal: Article] [CI: 3] [IF: 6.7]
DOI: 10.1042/CS20220656 SCOPUS: 85150001061

Manso J.A., Carabias A., Sárkány Z., de Pereda J.M., Pereira P.J.B., Macedo-Ribeiro S.
Pathogen-specific structural features of Candida albicans Ras1 activation complex: uncovering new antifungal drug targets. mBio14(4):e0063823, 2023. [Journal: Article] [CI: 2] [IF: 6,4 (*)]
DOI: 10.1128/mbio.00638-23 SCOPUS: 85169503311

Figueiredo F., Sárkány Z., Silva A., Vilasboas-Campos D., Maciel P., Teixeira-Castro A., Martins P.M., Macedo-Ribeiro S.
Drug repurposing of dopaminergic drugs to inhibit ataxin-3 aggregation. Biomedicine and Pharmacotherapy165:, 2023. [Journal: Article] [CI: 5] [IF: 6.9]
DOI: 10.1016/j.biopha.2023.115258 SCOPUS: 85166550618

Rodríguez-Blázquez A., Carabias A., Morán-Vaquero A., de Cima S., Luque-Ortega J.R., Alfonso C., Schuck P., Manso J.A., Macedo-Ribeiro S., Guerrero C., de Pereda J.M.
Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms. Cell communication and signaling : CCS21(1):, 2023. [Journal: Article] [CI: 8] [IF: 8,4 (*)]
DOI: 10.1186/s12964-023-01042-2 SCOPUS: 85147449404

Barbosa Pereira P.J., Manso J.A., Macedo-Ribeiro S.
The structural plasticity of polyglutamine repeats. Current Opinion in Structural Biology80:, 2023. [Journal: Review] [CI: 6] [IF: 6.1]
DOI: 10.1016/j.sbi.2023.102607 SCOPUS: 85159144967

Sárkány Z., Rocha F., Bratek-Skicki A., Tompa P., Macedo-Ribeiro S., Martins P.M.
Quantification of Surface Tension Effects and Nucleation-and-Growth Rates during Self-Assembly of Biological Condensates. Advanced Science10(23):, 2023. [Journal: Article] [CI: 2] [IF: 15,1 (*)]
DOI: 10.1002/advs.202301501 SCOPUS: 85160939519

Quaglia F., Meszáros B., Salladini E., Hatos A., Pancsa R., Chemes L.B., Pajkos M., Lazar T., Peña-Díaz S., Santos J., Ács V., Farahi N., Fichó E., Aspromonte M.C., Bassot C., Chasapi A., Davey N.E., Davidović R., Dobson L., Elofsson A., Erdos G., Gaudet P., Giglio M., Glavina J., Iserte J., Iglesias V., Kálmán Z., Lambrughi M., Leonardi E., Longhi S., Macedo-Ribeiro S., Maiani E., Marchetti J., Marino-Buslje C., Meszáros A., Monzon A.M., Minervini G., Nadendla S., Nilsson J.F., Novotný M., Ouzounis C.A., Palopoli N., Papaleo E., Pereira P.J.B., Pozzati G., Promponas V.J., Pujols J., Rocha A.C.S., Salas M., Sawicki L.R., Schad E., Shenoy A., Szaniszló T., Tsirigos K.D., Veljkovic N., Parisi G., Ventura S., Dosztányi Z., Tompa P., Tosatto S.C.E., Piovesan D.
DisProt in 2022: Improved quality and accessibility of protein intrinsic disorder annotation. Nucleic Acids Research50(D1):D480-D487, 2022. [Journal: Article] [CI: 125] [IF: 14,9]
DOI: 10.1093/nar/gkab1082 SCOPUS: 85125157608

Pinto M.F., Baici A., Pereira P.J.B., Macedo-Ribeiro S., Pastore A., Rocha F., Martins P.M.
interferENZY: A Web-Based Tool for Enzymatic Assay Validation and Standardized Kinetic Analysis. Journal of Molecular Biology433(11):, 2021. [Journal: Article] [CI: 5] [IF: 6,2]
DOI: 10.1016/j.jmb.2020.07.025 SCOPUS: 85089603828

Fraga J., Sárkány Z., Silva A., Correia I., Pereira P., Macedo-Ribeiro S.
Genetic code ambiguity modulates the activity of a C. albicans MAP kinase linked to cell wall remodeling. Biochimica et Biophysica Acta - Proteins and Proteomics1867(6):654-661, 2019. [Journal: Article] [CI: 5] [IF: 2,4]
DOI: 10.1016/j.bbapap.2019.02.004 SCOPUS: 85062145242

Silva A., Almeida B., Fraga J.S., Taboada P., Martins P.M., Macedo-Ribeiro S.
Distribution of Amyloid-Like and Oligomeric Species from Protein Aggregation Kinetics. Angewandte Chemie - International Edition56(45):14042-14045, 2017. [Journal: Article] [CI: 16] [IF: 12,1]
DOI: 10.1002/anie.201707345 SCOPUS: 85032264546

Ongoing Projects

Tackling Transthyretin to combat Diabetes-associated heart disease
Reference: ValidatioNN 2023 TinHeart
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Novo Nordisk
From 01-JUL-24 to 31-DEC-25
Interfacial modulation of protein solubility as a key to the discovery of new drugs targeting Amyotrophic Lateral Sclerosis
Reference: 2023.11892.PEX
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-FEB-25 to 31-JUL-26
Unveiling the potential of Neurotoxic Alpha-SYNuclein Oligomers as novel biomarkers and drug targets in Parkinson’s Disease
Reference: COMPETE2030-FEDER-00690800 - Projeto 15799
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JUL-25 to 29-JUN-28