creating a
healthier future

Biomolecular Structure & Function


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.



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.


Selected Publications

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: 1] [IF: 6,4 (*)]
DOI: 10.1128/mbio.00638-23 SCOPUS: 85169503311

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] [IF: 8,4 (*)]
DOI: 10.1186/s12964-023-01042-2 SCOPUS: 85147449404

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] [IF: 7,5 (*)]
DOI: 10.1016/j.biopha.2023.115258 SCOPUS: 85166550618

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: 1] [IF: 6,8 (*)]
DOI: 10.1016/ 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] [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., Davidovic 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: 86] [IF: 14,9]
DOI: 10.1093/nar/gkab1082 SCOPUS: 85125157608

Necci M., Piovesan D., Hoque M.T., Walsh I., Iqbal S., Vendruscolo M., Sormanni P., Wang C., Raimondi D., Sharma R., Zhou Y., Litfin T., Galzitskaya O.V., Lobanov M.Y., Vranken W., Wallner B., Mirabello C., Malhis N., Dosztányi Z., Erdos G., Mészáros B., Gao J., Wang K., Hu G., Wu Z., Sharma A., Hanson J., Paliwal K., Callebaut I., Bitard-Feildel T., Orlando G., Peng Z., Xu J., Wang S., Jones D.T., Cozzetto D., Meng F., Yan J., Gsponer J., Cheng J., Wu T., Kurgan L., Promponas V.J., Tamana S., Marino-Buslje C., Martínez-Pérez E., Chasapi A., Ouzounis C., Dunker A.K., Kajava A.V., Leclercq J.Y., Aykac-Fas B., Lambrughi M., Maiani E., Papaleo E., Chemes L.B., Álvarez L., González-Foutel N.S., Iglesias V., Pujols J., Ventura S., Palopoli N., Benítez G.I., Parisi G., Bassot C., Elofsson A., Govindarajan S., Lamb J., Salvatore M., Hatos A., Monzon A.M., Bevilacqua M., Micetic I., Minervini G., Paladin L., Quaglia F., Leonardi E., Davey N., Horvath T., Kovacs O.P., Murvai N., Pancsa R., Schad E., Szabo B., Tantos A., Macedo-Ribeiro S., Manso J.A., Pereira P.J.B., Davidovic R., Veljkovic N., Hajdu-Soltész B., Pajkos M., Szaniszló T., Guharoy M., Lazar T., Macossay-Castillo M., Tompa P., Tosatto S.C.E.,
Critical assessment of protein intrinsic disorder prediction. Nature Methods18(5):472-481, 2021. [Journal: Article] [CI: 142] [IF: 48]
DOI: 10.1038/s41592-021-01117-3 SCOPUS: 85104988931

Martins P.M., Navarro S., Silva A., Pinto M.F., Sárkány Z., Figueiredo F., Pereira P.J.B., Pinheiro F., Bednarikova Z., Burdukiewicz M., Galzitskaya O.V., Gazova Z., Gomes C.M., Pastore A., Serpell L.C., Skrabana R., Smirnovas V., Ziaunys M., Otzen D.E., Ventura S., Macedo-Ribeiro S.,
MIRRAGGE – Minimum Information Required for Reproducible AGGregation Experiments. Frontiers in Molecular Neuroscience13:, 2020. [Journal: Review] [CI: 15] [IF: 5,6]
DOI: 10.3389/fnmol.2020.582488 SCOPUS: 85097652573

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: 4] [IF: 6,2]
DOI: 10.1016/j.jmb.2020.07.025 SCOPUS: 85089603828

Fraga J.S., Sárkány Z., Silva A., Correia I., Pereira P.J.B., 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: 4] [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: 11] [IF: 12,1]
DOI: 10.1002/anie.201707345 SCOPUS: 85032264546

Ongoing Projects

Chemical activity of intrinsically disordered polypeptides that phase separate into neurotoxic biological colloids
Reference: PTDC/QUI-COL/2444/2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 31-DEC-24
Development of brain-targeted nanobodies for application in spinocerebellar ataxia type 3 therapy
Reference: Ataxia UK Research Grants 2021 - NanoSCA3
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Ataxia UK
From 01-SEP-22 to 31-AUG-24