Where Ideas Grow

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

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: 9] [IF: 12,1]
DOI: 10.1002/anie.201707345 SCOPUS: 85032264546

Merski M., Moreira C., Abreu R.M.V., Ramos M.J., Fernandes P.A., Martins L.M., Pereira P.J.B., Macedo-Ribeiro S.,
Molecular motion regulates the activity of the mitochondrial serine protease HtrA2. Cell Death and Disease8(10):, 2017. [Journal: Article] [CI: 13] [IF: 5,6]
DOI: 10.1038/cddis.2017.487 SCOPUS: 85031277139

Piovesan D., Tabaro F., Micetic I., Necci M., Quaglia F., Oldfield C.J., Aspromonte M.C., Davey N.E., Davidovic R., Dosztányi Z., Elofsson A., Gasparini A., Hatos A., Kajava A.V., Kalmar L., Leonardi E., Lazar T., Macedo-Ribeiro S., Macossay-Castillo M., Meszaros A., Minervini G., Murvai N., Pujols J., Roche D.B., Salladini E., Schad E., Schramm A., Szabo B., Tantos A., Tonello F., Tsirigos K.D., Veljkovic N., Ventura S., Vranken W., Warholm P., Uversky V.N., Dunker A.K., Longhi S., Tompa P., Tosatto S.C.E.,
DisProt 7.0: A major update of the database of disordered proteins. Nucleic Acids Research45(D1):D219-D227, 2017. [Journal: Article] [CI: 168] [IF: 11,6]
DOI: 10.1093/nar/gkw1056 SCOPUS: 85016112986

Matos C.A., Nóbrega C., Louros S.R., Almeida B., Ferreiro E., Valero J., De Almeida L.P., Macedo-Ribeiro S., Carvalho A.L.,
Ataxin-3 phosphorylation decreases neuronal defects in spinocerebellar ataxia type 3 models. Journal of Cell Biology212(4):465-480, 2016. [Journal: Article] [CI: 28] [IF: 8]
DOI: 10.1083/jcb.201506025 SCOPUS: 84959536774

Almeida B., Abreu I.A., Matos C.A., Fraga J.S., Fernandes S., Macedo M.G., Gutiérrez-Gallego R., Pereira P.J.B., Carvalho A.L., Macedo-Ribeiro S.,
SUMOylation of the brain-predominant Ataxin-3 isoform modulates its interaction with p97. Biochimica et Biophysica Acta - Molecular Basis of Disease1852(9):1950-1959, 2015. [Journal: Article] [CI: 30] [IF: 5,2]
DOI: 10.1016/j.bbadis.2015.06.010 SCOPUS: 84955513053

Scarff C.A., Almeida B., Fraga J., Macedo-Ribeiro S., Radford S.E., Ashcroft A.E.,
Examination of ataxin-3 (atx-3) aggregation by structural mass spectrometry techniques: A rationale for expedited aggregation upon polyglutamine (polyQ) expansion. Molecular and Cellular Proteomics14(5):1241-1253, 2015. [Journal: Article] [CI: 26] [IF: 5,9]
DOI: 10.1074/mcp.M114.044610 SCOPUS: 84929657616

Fraga J., Maranha A., Mendes V., Pereira P.J.B., Empadinhas N., Macedo-Ribeiro S.,
Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway. Scientific Reports5:8026, 2015. [Journal: Article] [CI: 11] [IF: 5,2]
DOI: 10.1038/srep08026 SCOPUS: 84923061324

Santos J.A., Alonso-Garciá N., Macedo-Ribeiro S., Barbosa Pereira P.J.,
The unique regulation of iron-sulfur cluster biogenesis in a Gram-positive bacterium. Proceedings of the National Academy of Sciences of the United States of America111(22):, 2014. [Journal: Article] [CI: 28] [IF: 9,7]
DOI: 10.1073/pnas.1322728111 SCOPUS: 84901821729

Rocha R., Pereira P.J.B., Santos M.A.S., Macedo-Ribeiro S.,
Unveiling the structural basis for translational ambiguity tolerance in a human fungal pathogen. Proceedings of the National Academy of Sciences of the United States of America108(34):14091-14096, 2011. [Journal: Article] [CI: 33] [IF: 9,7]
DOI: 10.1073/pnas.1102835108 SCOPUS: 80052182956

Matos C.A., de Macedo-Ribeiro S., Carvalho A.L.,
Polyglutamine diseases: The special case of ataxin-3 and Machado-Joseph disease. Progress in Neurobiology95(1):26-48, 2011. [Journal: Review] [CI: 96] [IF: 8,9]
DOI: 10.1016/j.pneurobio.2011.06.007 SCOPUS: 79960668226

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