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Protein Biochemistry and Biophysics Laboratory

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Protein Biochemistry and Biophysics Laboratory


About the PBBL

The Protein Biochemistry and Biophysics Laboratory (PBBL) is focused on the study of protein stability and folding and their implications in cell homeostasis in general and in protein aggregation that leads to neurodegeneration and disease. The current research activities encompass in vitro studies regarding the stability and activity of oxidoreductases, in particular those involved in oxidative protein folding, and, a cell biology approach using fluorescence microscopy and proteomics to address the mechanism of prion diseases and involvement of oxidative stress in cell toxicity and neurodegeneration.


Publications (2008-2017)

A.C.D. Plufck, D.P.C. de Barros, L.P. Fonseca, E.P. Melo* (2018) Stability of lipases in miniemulsion systems: Correlation between secondary structure and activity”, Enz. Microbiol. Technol. 114: 7-14.

E.P. Melo, C. Lopes, P. Gollwitzer, S. Lortz, S. Lenzen, I. Mehmeti, C. F. Kaminski, D. Ron, E. Avezov (2017) “Triper, an optical probe tuned to the endoplasmic reticulum tracks changes in luminal H2O2”, BMC Biology 15: 24.

Macedo, J.A., D. Schrama, I. Duarte, E. Tavares, J. Renault, M.E. Futschik, P.M. Rodrigues, E.P. Melo* (2017) “Membrane-enriched proteome changes and prion protein expression during neural differentiation and in neuroblastoma cells.” BMC Genomics 18: 319.

Anjos, L., I. Morgado, M. Guerreiro, J. C. Cardoso, E. P. Melo, D. M. Power (2017) “Cartilage Acidic Protein 1 (CRTAC1), a new member of the beta-propeller protein family with amyloid propensity”, Proteins 85: 242-255.

Konno, K., E. P. Melo, C. Lopes, C. F. Kaminski, I. Mehmeti, S. Lenzen, D. Ron, E. Avezov (2015) “ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4 mediated oxidative protein folding”, J. Cell Biol. 211: 253-259.

Estrela, N., H. G. Franquelim, C. Lopes, E. Tavares, J. A. Macedo, G. Christiansen, D. E. Otzen, E. P. Melo* (2015) “Sucrose prevents protein fibrillation through compaction of the tertiary structure but hardly affects the secondary structure”
Proteins 83: 2039-2051.

Avezov, E., T. Konno, A. Zyryanova, W. Chen, R. Laine, A. Crespillo-Casada, E. P. Melo, R. Ushioda, K. Nagata, C. F. Kaminski, H. P. Harding, D. Ron (2015) “Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulum”
BMC Biology 13: 2.

Tsunoda, S., E. Avezov, A. Zyryanova, T. Konno, L. Mendes-Silva, E. P. Melo, H. P. Harding, D. Ron (2014) “Intact protein folding in the glutathione-depleted endoplasmic reticulum implicates alternative protein thiol reductants”
eLife 3: e03421.

Tavares, E., J. A. Macedo, P. M. R. Paulo, C. Tavares, C. Lopes, E. P. Melo* (2014) “Live-cell FRET imaging reveals clustering of the prion protein at the cell surface induced by infectious prions” Biochim. Biophys. Acta – Molecular Basis of Disease 11: 744-751.

Brissos, V., N. Gonçalves, E. P. Melo, L. O. Martins (2014) “Directed evolution leads to aggregation-resistant variants with improved stability” PLOS One 9: e87209.

Rosa, M., C. Lopes, E. P. Melo, S. K. Singh, V. Geraldes, M. A. Rodrigues (2013). Measuring and modelling hemoglobin aggregation below freezing temperature J. Phys. Chem. B 117 8939 8946

Avezov, E., B. C. S. Cross, G. S. K. Schierle, M. Winters, H. P. Harding, E.P. Melo, C. F. Kaminski, D. (2013) Ron Lifetime imaging of a fluorescent protein sensor tracks ER thiol redox revealing its surprising stability J. Cell Biol. 201 337 349

Anjos, L., A. S. Gomes, E.P. Melo, A. V. M. Canário, D. M. Power. (2013) Cartilage acidic protein 2 a hyperthermostable, high affinity calcium-binding protein Biochim. Biophys. Acta – Proteins and Proteomics 1834 642 650

Fernandes, A.T., C. Lopes, L. O. Martins and E.P. Melo* (2012) Unfolding pathway of CotA-laccase and the role of cooper on the prevention of refolding through aggregation of the unfolded state Biochem. Biophys. Res. Commun 422 442 446

Fernandes, A.T., M. M. Pereira, C. S. Silva, P. F. Lindley, I. Bento, E. P. Melo* and L. O. Martins* (2011) “The removal of a disulfide bridge of CotA-laccase changes the slower motion dynamics involved in copper binding but has no effect on the thermodynamic stability” J. Biol. Inorg. Chem. 16: 641-651.

Melo, E.P., N. Estrela, C. Lopes, A. C. Matias, E. Tavares and V. Ochoa-Mendes (2010) “Compacting proteins: Pros and Cons od osmolyte-induced folding” Curr. Prot. Pep. Science 11: 744-751.

Zito, E., E.P. Melo, Y.Yang, Å. Wahlander, T.A. Neubert and D. Ron (2010) “Oxidative protein folding by an endoplasmic reticulum localized peroxiredoxin. Molec. Cell 40: 787-797.

Madeira, C. Estrela N., Ferreira JAB., Andrade SM., Costa, SMB., Melo EP. (2009), “Fluorescence lifetime imaging microscopy and fluorescence resonance energy transfer from cyan to yellow fluorescent protein validates a novel method to cluster proteins on solid surfaces”, Journal of Biomed Optics, 14(4):044035.

Morgado, I., Fernandes, AT; Martins, LO; Melo, EP (2009) “The hyperthermophilic nature of the metallo-oxidase from Aquifex aeolicus”, Biochim. Biophys. Acta- Proteins and Proteiomics 1794(1): 75-83.

E.P. Melo, E. Lundberg, N.L. Estrela, A.E. Samer-Eriksson and D. Power (2008) “Piscine transthyretin hormone affinity and fibril formation: The role of the N-terminal”, Mol. Cell. Endocrinol. 295: 48-58.

Brissos, V., E.P. Melo, J.M.G. Martinho and J.M.S. Cabral (2008) “Biochemical and Structural Characterisation of Cutinase Mutants in the Presence of the Anionic Surfactant AOT”, Biochim. Biophys. Acta 1784: 1326-1334.

Baptista, R.P., S.H. Pedersen, G.J.M. Cabrita, D.E. Otzen, J.M.S. Cabral and E.P. Melo(2008) “Thermodynamics and Mechanism of Cutinase Stabilization by Trehalose” Biopolymers 89(6):538-547.

Durão, P., Z. Chen, A.T. Fernandes, M.M. Pereira, E.P. Melo, and L.O. Martins (2008) “Copper Incorporation Into Recombinant CotA-laccase from Bacillus subtilis: Characterization of Cu Full-Loaded Enzymes”. J. Biol. Inorg. Chem. 13 (2):183-193.


Project Grants

2017/2018 – Cryocube – Portugal 2020 – “Desenvolvimento de tecnologia criogénica para substâncias biológicas”.

PTDC/CTM-NAN/2700/2012 – “Nano-Dímeros Metálicos para Biosensores de Proteína Individual com Resposta Plasmónica Intensificada”, Team member

PTDC/QUI-BIQ/119677/2010 – “A biophysical approach to oxidative protein folding in the endoplasmic reticulum”, Principal Investigator

PTDC/EQU-EQU/104318/2008 – “Controlled freezing to improve the stability and delivery of therapeutic proteins”, Team member.

PTDC/QUI/73027/2006 – “Single-Molecule Detection of the Prion Protein: Characterization of Conformational Changes Involved in Prion Diseases”, Coordinator.

POCI/CVT/56668/2004 “A Murine Neuroblastoma Cell-Based Approach to Study and Prevent Prion Diseases”, Principal Investigator.

PTDC/QUI/64658/2006 – “Single Molecule Signalling of peptide metal binding”. Team member

PTDC/QUI/64112/2006 – “Transferência Electrónica fotoinduzida por proteínas hémicas artificiais em sistemas de nanotubos de carbono”. Team member.

POCI/QUI/58816/2004 “Lipid-Lipid and Protein-Lipid Interactions in Model Systems of Cell Membranes”. Team member.

POCI/QUI/57387/2004 “Molecular Organization of Functionalized Porphyrins in Giant Vesicles and Supramolecules” . Team member.

Sapiens 2002, Portugal. “Relation Between CYP3A4 Gene Polymorphism, Protein Structure and Activity in Disease Setting”, Team Member.

Sapiens 2002, Portugal. “Design of Stabilizing Affinity Molecular Probes: A Practical Approach to Assess and Enhance Protein Stability”, Team Member.


Representative Images



Stable cell clone expressing a fusion between the prion protein and the yellow fluorescent protein attached to the outer surface of the cell membrane. Nuclei labelled with Hoechst 33342 in blue and endoplamic reticulum labelled with ER-tracker red (from Tavares et al., 2014).

Time course of in vivo fluorescence excitation ratio of HyPer and TriPer expressed in the endoplasmic reticulum to detect the reactive oxygen species hydrogen peroxide (from Melo et al., 2017).